Kinesins in Health and Disease:
Emerging Roles in Neurodegeneration and Cancer
Kajal Pansare1*, Ganesh Sonawane1, Chandrashekhar Patil2, Deepak Sonawane3,
Sunil Mahajan3, Deepak Somavanshi4, Yogesh Ahire4, Vinod Bairagi5
1Assistant Professor, Divine College of Pharmacy, Satana, Dist. Nashik - 423301, India.
2Associate Professor, Divine College of Pharmacy, Satana, Dist. Nashik - 423301, India.
3Professor, Divine College of Pharmacy, Satana, Dist. Nashik - 423301, India.
4Associate Professor, KBHSS Trust’s Institute of Pharmacy, Malegaon, Dist. Nashik - 423105, India.
5Professor, KBHSS Trust’s Institute of Pharmacy, Malegaon, Dist. Nashik - 423105, India.
*Corresponding Author E-mail: kajalgsonawane@gmail.com
ABSTRACT:
Kinesin proteins are ATP-dependent motor proteins that drive intracellular transport, mitotic spindle formation, and organelle positioning along microtubules. Kinesins are essential for cellular organization, particularly in neurons, as they transport critical cargo such as vesicles and mitochondria. Dysfunction of kinesins is increasingly linked to diseases such as neurodegeneration and cancer. In neurodegenerative disorders like Alzheimer’s, Parkinson’s, and Amyotrophic Lateral Sclerosis (ALS), mutations in kinesins (e.g., KIF5A, KIF1A, KIF1B) impair axonal transport and mitochondrial function, contributing to neuronal loss. While, in cancers, overexpression of mitotic kinesins such as KIF11, KIF15, and KIF20A promotes unchecked proliferation and genomic instability. These proteins are now being investigated as therapeutic targets, with several inhibitors under development. This review summarizes kinesin structure and function, their roles in disease pathogenesis, and current therapeutic strategies. It also explores the potential of kinesins as diagnostic biomarkers and highlights ongoing challenges, including the need for better in vivo models and interdisciplinary approaches. Overall, kinesins represent a critical molecular link between neurodegeneration and cancer, offering opportunities for dual-disease targeting.
KEYWORDS: Kinesin proteins, Intracellular transport, Neurodegenerative diseases, Cancer, Microtubule dynamics, Axonal transport, Therapeutic targets.
1. INTRODUCTION:
Cellular function and survival depend on the precise distribution of organelles and proteins, a task primarily managed by the microtubule network and associated motor proteins1,2. Among these, kinesins are key ATP-dependent motors that typically move cargo toward the microtubule plus-end, supporting essential processes such as vesicle transport, organelle positioning, and mitosis3. Discovered in the 1980s in squid axoplasm, kinesins have since been classified into 14 families (Kinesin-1 to Kinesin-14), comprising 45 human genes collectively known as KIFs. While all kinesins share a conserved motor domain, their tail domains differ, enabling cargo specificity and regulatory diversity4.
Kinesins are particularly vital in neurons, where they support axonal transport and synaptic integrity, and in dividing cells, where they regulate spindle formation and chromosome segregation5. Dysregulation of kinesin function is increasingly linked to disease: mutations disrupt neuronal transport in neurodegenerative disorders, while overexpression of mitotic kinesins drives uncontrolled proliferation in cancer6,7. This review explores the structure, classification, and diverse roles of kinesins, emphasizing their dual impact in neurodegeneration and tumor progression.
2. Kinesin Superfamily: Structure and Classification:
The kinesin superfamily comprises a group of evolutionarily conserved motor proteins that move along microtubules using the energy derived from ATP hydrolysis. These proteins share a common structural framework but exhibit diverse cellular roles, determined by variations in their domain architecture and regulatory elements.
2.1 Structural Features of Kinesins:
Most kinesins have a modular structure consisting of four main regions. The motor domain (head), a highly conserved N-terminal or central domain (~340 amino acids), is responsible for ATP binding, hydrolysis, and interaction with microtubules, determining movement direction. The neck linker, located adjacent to the motor domain, acts as a mechanical lever that controls the direction and processivity of movement, propelling the trailing head forward in a hand-over-hand mechanism. The stalk (coiled-coil region), made of coiled-coil α-helices, facilitates kinesin dimerization and structural rigidity, influencing its navigation through cellular environments. Finally, the tail domain contains cargo-binding motifs and interacts with adaptor proteins, determining cargo specificity and enabling the transport of various intracellular components8.
2.2 Classification of Kinesins (Kinesin-1 to Kinesin-14):
The human genome encodes 45 kinesin genes, grouped into 14 families (Kinesin-1 to Kinesin-14) based on phylogenetic relationships of their motor domains. These families differ in motor location (N-terminal, internal, or C-terminal), cargo types, directionality, and biological function, as shown in Table 1.
Kinesin-1, also known as conventional kinesin, is primarily involved in transporting organelles and vesicles, especially in neurons, with key members including KIF5A and KIF5B. Kinesin-2 participates in intraflagellar transport and typically operates as part of a heterotrimeric complex. Kinesin-3 family members, such as KIF1A and KIF1B, are highly processive and play critical roles in transporting synaptic vesicles and endosomes. Families Kinesin-4 through Kinesin-10 serve a range of functions including chromosome alignment, mitotic spindle assembly, nuclear migration, and cytokinesis—for example, KIF11 (also known as Eg5) in Kinesin-5 and KIF18A in Kinesin-8. Kinesin-11 through Kinesin-14 are more specialized, with Kinesin-14 representing a unique subgroup that moves toward the minus-end of microtubules, in contrast to the predominantly plus-end directed kinesins. Kinesin-14 members, such as KIFC1, are especially important for organizing the mitotic spindle.
2.3 Directionality of Movement:
The majority of kinesins move toward the plus-end of microtubules (away from the nucleus, toward the cell periphery), facilitating anterograde transport of cargo. However, Kinesin-14 family members (e.g., KIFC1) move toward the minus-end, contributing to retrograde transport and mitotic spindle assembly. Directionality is determined by the orientation of the motor domain and neck linker relative to the microtubule lattice.
Table 1: Kinesin Superfamily Classification
Kinesin Family |
Examples |
Function |
Directionality |
Key Roles |
Kinesin-1 (Conventional Kinesins) |
KIF5A, KIF5B |
Organelle and vesicle transport, especially in neurons |
Plus-end directed (toward cell periphery) |
Neuronal transport, synaptic maintenance, vesicle trafficking |
Kinesin-2 |
KIF3A, KIF3B |
Intraflagellar transport, heterotrimeric complexes |
Plus-end directed |
Ciliary and flagellar function |
Kinesin-3 |
KIF1A, KIF1B |
Synaptic vesicle and endosome transport |
Plus-end directed |
Neuronal transport, synaptic vesicle trafficking |
Kinesin-4 to Kinesin-10 |
KIF11 (Eg5), KIF18A |
Chromosome alignment, spindle formation, nuclear migration, cytokinesis |
Mostly Plus-end directed (Eg5 is minus-end directed) |
Mitosis, chromosome segregation, spindle dynamics |
Kinesin-11 to Kinesin-14 |
KIFC1 |
Mitotic spindle organization |
Minus-end directed (exception to mostly plus-end direction) |
Spindle organization, mitosi |
2.4 Tissue-Specific Expression and Regulation:
Kinesins display tissue-specific expression aligned with their functions. Neuronal kinesins (e.g., KIF1A, KIF5A) support long-range axonal transport, while mitotic kinesins (e.g., KIF11, KIF20A) are active in dividing cells, aiding spindle assembly. Ciliary kinesins (e.g., KIF3A/B) function in epithelial tissues for intraflagellar transport. Their activity is regulated by phosphorylation, autoinhibition, and adaptor proteins, enabling precise control of motor function. This specialization and regulation equip kinesins to perform diverse roles in both health and disease9.
3. Kinesins in Normal Cellular Function:
Kinesins are indispensable for the proper functioning of eukaryotic cells. By converting chemical energy from ATP hydrolysis into mechanical work, these motor proteins facilitate the intracellular transport of cargo, orchestrate cell division, and maintain specialized cellular structures such as cilia and neuronal processes. Below is a detailed account of their key physiological roles:
3.1 Organelle and Vesicle Transport:
Kinesins play a crucial role in transporting cellular cargo along microtubules, directing it toward the cell periphery. Kinesin-1 and Kinesin-3 families (e.g., KIF5A, KIF5B, KIF1A, KIF1B) are key in transporting mitochondria, endosomes, lysosomes, and secretory vesicles, which are vital for energy supply, cellular trafficking, and protein delivery. These kinesins work with adaptor proteins to recognize cargo. Disruptions in this transport system can lead to organelle mislocalization, cellular stress, and impaired function, particularly in polarized cells like neurons.
3.2 Mitosis and Chromosome Segregation:
Kinesins are crucial for mitosis, ensuring accurate chromosome segregation and spindle dynamics. Kinesin-5 (e.g., KIF11/Eg5) crosslinks microtubules to maintain bipolar spindles, while Kinesin-13 (e.g., KIF2A, KIF2C) depolymerizes microtubules and regulates kinetochore-microtubule attachment during anaphase. Kinesin-14 (e.g., KIFC1) focuses the spindle and balances forces during metaphase. Kinesin-4 and Kinesin-10 families aid in chromosome alignment and movement along microtubules. Defects in these kinesins can cause chromosomal instability and contribute to tumorigenesis10.
3.3 Cilia and Flagella Function:
Cilia and flagella, essential for cell motility and signaling, rely on intraflagellar transport (IFT) for assembly and maintenance, a process powered by specific kinesins. The Kinesin-2 family, particularly the KIF3A/KIF3B heterodimers, is responsible for anterograde transport of IFT particles and structural proteins from the base to the tip of cilia and flagella. Additionally, kinesins from the Kinesin-9 and Kinesin-17 families contribute to flagellar motility and maintenance in some species. Disruptions in kinesin function can impair ciliogenesis, leading to ciliopathies—disorders that include developmental defects, renal cysts, respiratory dysfunction, and infertility, such as primary ciliary dyskinesia and Bardet-Biedl syndrome.
3.4 Neuronal Transport and Synaptic Maintenance:
Neurons are highly dependent on kinesin-mediated transport for axon development, synaptic plasticity, and neurotransmission. Kinesin-1 (e.g., KIF5A) transports mitochondria and synaptic vesicle precursors along axons, while Kinesin-3 (e.g., KIF1A, KIF1B) is essential for transporting synaptic vesicle proteins. Kinesin-2 and Kinesin-4 contribute to dendritic transport and receptor localization. Proper kinesin function is crucial for synaptic homeostasis, neurotrophic signaling, and axon integrity. Impaired transport due to kinesin mutations is linked to neurodegenerative diseases, highlighting the importance of kinesins in maintaining cellular processes and their role in disease mechanisms11.
4. Kinesins in Neurodegenerative Diseases:
Neurodegenerative diseases are characterized by progressive loss of neuronal function and structure, often due to impaired axonal transport, mitochondrial dysfunction, protein aggregation, and inflammation. Given their crucial roles in neuronal cargo transport, kinesins—particularly KIF family members—have emerged as central players in the pathogenesis of disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS).
4.1 Alzheimer’s Disease (AD):
Alzheimer’s disease is the most common form of dementia, marked by memory loss, synaptic failure, and neuronal death. Disruption of intracellular transport is a prominent early feature of AD.
· Impaired Axonal Transport: Efficient axonal transport is essential for maintaining synaptic function and neuronal viability. In AD, defective transport mechanisms precede plaque and tangle formation, resulting in synaptic dysfunction. Microtubule disruption, oxidative stress, and abnormal phosphorylation of transport proteins contribute to this dysfunction.
· KIF5 Dysfunction and Tau Pathology: KIF5 (Kinesin-1 family), particularly KIF5A, is crucial for transporting mitochondria and synaptic vesicles along axons. In AD hyperphosphorylated tau, a microtubule-associated protein, detaches from microtubules and aggregates into neurofibrillary tangles. This disrupts kinesin binding sites on microtubules, hindering KIF5-mediated transport. Additionally, tau has been shown to directly inhibit kinesin movement, further compromising cargo delivery.
· Amyloid Precursor Protein (APP) Transport: Kinesins, especially KIF5, are involved in anterograde transport of APP-containing vesicles. Impairment in APP trafficking leads to its aberrant cleavage by β- and γ-secretases, increasing the production of amyloid-β (Aβ) peptides. Accumulation of Aβ aggregates exacerbates oxidative stress, impairs synaptic function, and contributes to neuronal death12.
4.2 Parkinson’s Disease (PD):
Parkinson’s disease is a movement disorder caused by dopaminergic neuron degeneration in the substantia nigra. Mitochondrial dysfunction and defective transport are pivotal in its pathogenesis.
· Mitochondrial Transport and KIF1B, KIF5A: Neurons depends on proper mitochondrial distribution for energy and calcium buffering. In PD, KIF1B and KIF5A mediate anterograde mitochondrial transport along axons. Impaired kinesin function causes energy failure at synapses, increased ROS, and vulnerability to degeneration.
· Links with PINK1, Parkin, and Mitophagy: PINK1 and Parkin are crucial for mitophagy, the process by which damaged mitochondria are degraded. Mutations in PINK1/Parkin result in accumulation of dysfunctional mitochondria, which are poorly transported due to defective kinesin-mitochondria interactions. Recent studies suggest PINK1/Parkin also regulate kinesin detachment from damaged mitochondria, balancing removal versus transport. Dysregulation leads to axonopathy and synaptic degeneration, hallmarks of PD.
4.3 Amyotrophic Lateral Sclerosis (ALS): ALS is a progressive neurodegenerative disorder that affects motor neurons, leading to muscle weakness, atrophy, and eventual paralysis.
· KIF5A Mutations: KIF5A has been identified as a causative gene in familial ALS. Mutations often occur in the tail domain, affecting cargo binding and transport specificity. KIF5A dysfunction leads to defective axonal transport of mitochondria, RNA granules, and neurofilaments.
· Disrupted Axonal Trafficking and Neuroinflammation: Axonal transport disruption in ALS contributes to distal axon degeneration, which progresses retrogradely to the cell body ("dying-back neuropathy"). Defective organelle transport induces cellular stress, activating inflammatory pathways. Neuroinflammation, involving activated microglia and astrocytes, exacerbates neuronal damage. Accumulation of mislocalized proteins (e.g., TDP-43) due to impaired kinesin transport further contributes to toxicity13,14.
5. Kinesins in Cancer:
Kinesins, particularly those involved in mitosis and cell division, are critical players in cancer biology. These motor proteins are implicated in regulating cell proliferation, mitotic progression, metastasis, and genomic stability. Aberrant expression and dysregulation of certain kinesins have been linked to the initiation and progression of various cancers. Furthermore, targeting kinesins offers a promising approach for cancer therapy, though challenges like drug resistance and off-target effects remain significant obstacles15.
5.1 Oncogenic Kinesins and Overexpression:
In cancer, the overexpression of certain kinesins is often observed, which directly contributes to tumorigenesis and the promotion of aggressive tumor behaviors. Specifically, kinesins like KIF11 (Eg5), KIF15, and KIF20A play crucial roles in mitotic progression and cell division, two processes often dysregulated in cancer.
· KIF11 (Eg5) is essential for spindle formation and separation during mitosis. It helps maintain mitotic spindle integrity, and its overexpression leads to increased cell proliferation and mitotic progression, often resulting in chromosomal instability. High expression of Eg5 is associated with poor prognosis and is a target for drugs like monastrol, which inhibits its function.
· KIF15 is involved in the mitotic spindle assembly and chromosome segregation. Overexpression of KIF15 has been noted in multiple cancers, such as breast cancer, where it supports the progression of mitosis and cell cycle dynamics.
· KIF20A is associated with cytokinesis and ensures the completion of cell division. It has been implicated in solid tumors like lung, liver, and colon cancers, where its overexpression is correlated with poor prognosis and tumor recurrence.
5.2 Mechanisms of Tumor Progression:
Kinesins are critical for several processes in cancer progression, including cell cycle regulation, angiogenesis, and metastasis. These processes are essential for the expansion of primary tumors, their infiltration into surrounding tissues, and the formation of secondary metastatic lesions.
· Cell Cycle Progression: Kinesins regulate crucial events during the cell cycle, especially mitosis. Overactive or mutated kinesins like KIF11 and KIF20A result in increased mitotic entry, leading to uncontrolled cell division. In addition, cytokinesis defects caused by altered kinesin function contribute to chromosomal instability and the generation of polyploid cells, which promote tumorigenesis.
· Angiogenesis: Kinesins like KIF14 are involved in endothelial cell division and blood vessel formation. Tumors require a vascular supply to sustain growth and metastasis. Overexpression of certain kinesins in endothelial cells leads to abnormal angiogenesis, which facilitates tumor growth and provides a pathway for tumor cells to enter the bloodstream.
· Metastasis: The ability of cancer cells to migrate and invade distant tissues is another critical aspect of tumor progression. Kinesins such as KIF5 help promote cell motility and migration through interactions with microtubules and extracellular matrix components. These kinesins support the process of invasion and survival in metastatic sites, contributing to the dissemination of cancer cells throughout the body.
· Crosstalk with Oncogenic Signaling Pathways: Kinesins are regulated by and interact with various oncogenic signaling pathways, such as PI3K/AKT, MAPK, and p53. For instance, the PI3K/AKT pathway enhances cell survival and migration, promoting tumor growth and progression. Kinesins like KIF20A are regulated by this pathway, impacting cell division and mitotic progression. Similarly, the MAPK pathway, which is involved in cell cycle regulation, modulates the function of kinesins during mitosis. Disruption in these signaling pathways leads to uncontrolled tumor cell proliferation and metastasis.
5.3 Targeting Kinesins in Cancer Therapy:
Given their critical roles in cell division and tumor progression, kinesins have emerged as promising therapeutic targets in cancer. Several inhibitors of kinesins, especially those targeting Eg5 (KIF11), have shown preclinical promise, and clinical trials are ongoing.
Kinesin Inhibitors:
· Monastrol: Monastrol is a selective Eg5 inhibitor that disrupts the mitotic spindle and induces mitotic arrest, ultimately leading to cell death. Preclinical studies and early-phase clinical trials have demonstrated its potential against various cancers, including ovarian and breast cancer.
· Ispinesib: Another Eg5 inhibitor, ispinesib has shown antitumor activity in clinical trials, particularly in metastatic breast cancer. It works by halting mitosis in cancer cells, leading to their death. However, resistance and toxicity remain challenges in its use16.
6. Cross-Talk between Neurodegeneration and Cancer:
Despite appearing as two vastly different pathologies, neurodegeneration and cancer share a surprising number of molecular and cellular pathways. Both diseases involve dysregulation of fundamental biological processes such as cell cycle control, apoptosis, mitochondrial dynamics, and intracellular transport—areas where kinesin motor proteins play critical roles. Interestingly, while these shared pathways may drive proliferation in cancer, they often result in cell death and degeneration in neurodegenerative diseases, reflecting opposing pathological outcomes from common molecular dysfunctions.
6.1 Shared Pathways: Cell Cycle Control and Mitochondrial Dynamics
Kinesins are tightly linked to two major shared pathways implicated in both cancer and neurodegeneration:
· Cell Cycle Regulation: In cancer, dysregulation of the cell cycle leads to uncontrolled proliferation, often due to kinesin overexpression (e.g., KIF11, KIF20A). In contrast, in neurons—post-mitotic cells that do not divide—reactivation of the cell cycle is often aberrant and leads to apoptotic cell death, a feature observed in Alzheimer’s and Parkinson’s disease. Misexpression of cell cycle-associated kinesins in neurons may trigger DNA damage, oxidative stress, and eventual neurodegeneration.
· Mitochondrial Transport and Dynamics: Mitochondrial dysfunction is central to both disease classes. Kinesins such as KIF5B and KIF1B regulate mitochondrial trafficking along microtubules. In neurons, proper mitochondrial distribution is critical for synaptic function and survival. In diseases like ALS and Parkinson’s, defective mitochondrial movement contributes to energy deficits and axon degeneration. In cancer, altered mitochondrial dynamics support metabolic reprogramming and survival under stress, facilitating tumor progression.
6.2 Opposing Outcomes: Proliferation vs. Degeneration:
Although neurodegeneration and cancer share overlapping molecular pathways, their outcomes are fundamentally opposite. In cancer, kinesin dysregulation—such as overactivation of mitotic motors like KIF11 and KIF15—drives uncontrolled proliferation and evasion of apoptosis. In contrast, in neurodegenerative diseases, similar disruptions—like impaired mitochondrial transport or aberrant cell cycle re-entry—lead to neuronal dysfunction and death. Neurons, being highly polarized and energy-demanding, are particularly vulnerable to such transport failures, resulting in synaptic loss and cognitive decline. This contrast reflects a "biological trade-off," where mechanisms that favor replication in cancer may contribute to degeneration in neurons when misregulated.
6.3 Potential of Kinesins as Dual-Disease Biomarkers:
Kinesins are emerging as promising dual-purpose biomarkers and therapeutic targets in both neurodegeneration and cancer. For example, KIF5A mutations are linked to ALS and its altered expression is noted in certain cancers, while KIF1B is involved in both neuronal survival and neuroblastoma suppression. Their expression profiles may help distinguish between disease subtypes and offer insight in complex cases like paraneoplastic syndromes. Moreover, kinesin-based biomarkers could aid in early diagnosis, disease monitoring, and personalized therapy development across both conditions17.
7. Emerging Research and Therapeutic Potential:
With growing understanding of the diverse roles kinesins play in both physiological and pathological conditions, new therapeutic strategies are being developed to modulate kinesin function for clinical benefit. These include gene-targeting technologies, small molecule modulators, and approaches in personalized medicine, particularly for diseases like cancer and neurodegeneration where kinesins are increasingly recognized as critical players (Shown in Figure 1). This section explores the frontiers of kinesin-based therapeutic development and its potential for shaping future treatment paradigms.
7.1 Gene-targeting technologies:
CRISPR-Cas9 and RNA interference (RNAi) enable precise manipulation of kinesin genes like KIF11 and KIF5A, aiding in understanding their roles in disease mechanisms. RNAi knockdown of KIF20A can induce mitotic arrest in cancer cells, while correcting axonal transport deficits in neurodegenerative models18.
7.2 Small Molecule Modulators:
Drugs like monastrol, ispinesib, and filanesib target kinesins like KIF11, causing mitotic defects and tumor cell death. However, challenges such as drug resistance and off-target toxicity persist. Allosteric modulators are emerging as a promising strategy for more refined control, particularly for neurodegenerative conditions19.
7.3 Personalized Medicine and Biomarker Development:
Kinesins are increasingly used as biomarkers for cancer prognosis and neurodegenerative diseases. For instance, KIF20A and KIF5A mutations help stratify patients for tailored treatments, with molecular profiling becoming crucial for guiding therapy choices in oncology and neurology20.
8. Future Directions and Challenges:
Kinesins are pivotal in both normal cellular functions and disease processes like cancer and neurodegeneration. Yet, turning this knowledge into clinical impact presents several challenges
Figure 1: Emerging Strategies in Kinesin-Based Therapies
8.1 Unresolved Questions:
Key gaps remain in understanding how kinesins are regulated, particularly via post-translational modifications and cargo adaptor interactions. It's still unclear whether kinesin dysfunction is a cause or consequence in neurodegeneration, and the roles of several kinesins in cancer (e.g., KIF14, KIF18B) need further study.
8.2 In Vivo Models and Translation:
Most findings come from in vitro work, with a need for better in vivo models (e.g., mouse, zebrafish, Drosophila) to explore physiological roles. Translating kinesin-targeted therapies into the clinic faces hurdles like drug delivery, selectivity, and safety, requiring more robust preclinical and biomarker studies21.
8.3 Interdisciplinary Opportunities:
Kinesin research benefits from collaboration across fields such as neuroscience, oncology, and computational biology. Technologies like AI, super-resolution imaging, and systems biology can accelerate discovery and drug development. Cross-disciplinary teamwork will be crucial to move from basic science to clinical solutions22.
9. CONCLUSION:
Kinesins are fundamental to intracellular transport, mitosis, and neuronal function, making them essential for maintaining cellular homeostasis. Their dysfunction is increasingly linked to the pathogenesis of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and ALS, as well as to cancer progression and metastasis. This dual involvement underscores their potential as both biomarkers and therapeutic targets. While several small molecule inhibitors and genetic tools show promise, challenges like drug specificity, resistance, and incomplete mechanistic understanding remain. Therefore, further research into kinesin biology, supported by in vivo studies and interdisciplinary approaches, is critical to translating these insights into effective clinical applications.
10. REFERENCES:
1. Vale RD. The molecular motor toolbox for intracellular transport. Cell. 2003; 112(4):467–80.
2. Hirokawa N, Noda Y, Tanaka Y, Niwa S. Kinesin and dynein superfamily proteins and their molecular mechanisms of intracellular transport. Science. 2009; 305(5685): 331–6.
3. Cai D, Qiu J, Tamano H, et al. Axonal transport and neurodegenerative diseases. J Clin Invest. 2009;119(9):2658–64.
4. Mischerikow N, Le Guennec E, Karczewski J, et al. Microtubule dynamics and their role in mitosis and cell division. Nat Cell Biol. 2010; 12(4): 468–75.
5. Scholey JM, Verhey KJ, Schnapp BJ, et al. Kinesins: The motor proteins of the cytoskeleton. Nat Rev Mol Cell Biol. 2011; 12(10): 616–27.
6. Wang Z, Jiang X, Yang Z. Kinesin superfamily proteins in intracellular transport and mitosis. Nat Rev Mol Cell Biol. 2000; 1(3): 245–55.
7. Rosenfeld SS, Grossman S, Sontag ED, et al. Intracellular transport and mitosis: The role of kinesin. Biochim Biophys Acta. 2005; 1744(3): 444–53.
8. Huang J, Cialdella S, Kapoor TM. Structural and functional evolution of the kinesin motor domain. J Cell Biol. 2017; 216(3): 101–14.
9. Hackney DD, Sheetz MP. Kinesin family of motor proteins: Molecular mechanisms of transport and function. Nat Rev Mol Cell Biol. 2005; 6(12): 876–89.
10. Zhang F, Li Y, Zhang X, et al. Role of kinesins in cellular organization and intracellular trafficking. Cell Mol Life Sci. 2018;75(7):1279–87.
11. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 6th ed. New York: Garland Science; 2015.
12. Moreno H, Zhu Y, Wang X, et al. Impaired axonal transport and its role in neurodegenerative diseases. J Neurosci. 2020;40(12):3240–55.
13. Cai Q, Lu B. Kinesin-1 and kinesin-3 in neurodegenerative disease pathogenesis. Neurobiol Aging. 2014; 35(3): 555–63.
14. Kapitein LC, Wulf PS, Schonewille M, et al. The role of kinesin-1 in axonal transport and neurodegenerative diseases. Sci Signal. 2010; 3(137): ra75.
15. Mistry AM, Liao M, Aday S, et al. Targeting kinesin-5 in cancer therapy. Cancer Res. 2019; 79(5): 950–60.
16. Weaver BA, Silk AD, Roush WR, et al. Kinesin-5 inhibitors and their role in cancer therapy. Cell Cycle. 2007; 6(6): 838–44.
17. Seo J, Park M. Molecular crosstalk between cancer and neurodegenerative diseases. Cell Mol Life Sci. 2020; 77(14): 2659–80.
18. Morris RL, Scholey JM. Gene editing and RNAi targeting kinesins in cancer and neurodegeneration. Nat Rev Drug Discov. 2020;19(4):345–58.
19. Swan EM, Rix U, Smith AB, et al. small molecule modulators of kinesin activity in neurodegenerative diseases. Pharmacol Res. 2021; 163: 105229.
20. Verhey KJ, Rapoport TA. Kinesins: Motor proteins in the cytoskeleton. Cold Spring Harb Perspect Biol. 2011; 3(5): a004723.
21. Yun J, Lee H, Kim Y, et al. Challenges in targeting kinesins for therapeutic development. J Med Chem. 2022; 65(9): 5912–27.
22. Dong G, Luo D, Xie Z. Emerging therapeutic approaches targeting kinesins in neurodegenerative diseases and cancer. Trends Pharmacol Sci. 2019; 40(2): 132–46.
Received on 08.05.2025 Revised on 31.05.2025 Accepted on 17.06.2025 Published on 22.07.2025 Available online from July 26, 2025 Res.J. Pharmacology and Pharmacodynamics.2025;17(3):199-205. DOI: 10.52711/2321-5836.2025.00033 ©A and V Publications All right reserved
|
|
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License. |