ROLE OF MOTOR PROTEINS IN NEURODEGENERATIVE DISEASES

Year 2024, Volume: 44 Issue: 3, 263 - 274, 01.09.2024

Fatma Nur Zobar , Zekiye Tuba Tüylü Küçükkılınç

https://doi.org/10.52794/hujpharm.1509048

Abstract

Neurodegenerative diseases are associated with various risk factors such as heredity, age, and lifestyle. Numerous studies have proven that motor proteins and disruptions in axonal transport play significant roles in the pathway leading to neurodegenerative diseases. Motor proteins are dynamic structures that move toward the (+) and (-) ends of microtubules in neuronal cells to promote axonal transport and intracellular communication. Axonal transport abnormalities are linked to the existence of protein aggregates, which lead to neurodegeneration in a variety of neurodegenerative illnesses, including Huntington's disease, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Motor proteins, including as kinesins and dyneins, are in charge of axonal transport, which is an energy-dependent mechanism that transports cargoes like proteins, organelles, RNA, and synaptic vesicles between the cell body and axon terminals. Axonal transport is an important mechanism for neurons, which have a relatively large volume and are required to maintain intracellular homeostasis. Impaired axonal transport, abnormalities in the genes encoding axonal transport elements, or problems with energy production or use can impede intracellular communication, disrupt intercellular communication, and cause neuronal death. Irreversible and progressive neuronal losses can cause neurodegeneration, which leads to the onset of neurodegenerative disorders.

Keywords

Neurodegenerative diseases, motor proteins, axonal transport, kinesin, dynein

MOTOR PROTEİNLERİN NÖRODEJENERATİF HASTALIKLARDAKİ ROLÜ

Abstract

Nörodejeneratif hastalıkların görülme sıklığı günümüzde artmaya ve birçok insanı etkilemeye devam etmektedir. Nörodejeneratif hastalılar kalıtım, yaş, yaşam tarzı gibi farklı risk faktörleri ile ilişkilendirilmektedir. Yapılan birçok çalışma ile motor proteinler ve aksonal taşınmadaki bozuklukların, nörodejenerasyona ve nörodejeneratif hastalıklara sebep olan yolakta önemli rolleri olduğu kanıtlanmıştır. Motor proteinler, nöronal hücrelerde mikrotübülün (+) ve (-) uçlarına yürüyerek hücre içi iletimi ve aksonal taşınmayı sağlayan dinamik yapılardır. Yapılan incelemelerde, nörodejeneratif hastalığa sahip insan ve hayvan beyinlerinde, motor protein mekanizmasında bozuklukların olduğuna rastlanmıştır. Alzheimer, Parkinson, Amyotrofik Lateral Sklerozis ve Huntington Hastalığı gibi farklı nörodejeneratif hastalıklarda; nörodejenerasyona sebep olan protein agregatların varlığı aksonal taşınmadaki bozukluklar ile ilişkilendirilmektedir. Motor proteinler olan kinesin ve dineinler; protein, organel, RNA, sinaptik veziküller gibi kargoların hücre gövdesi ve akson uçları arasında taşınmasını sağlayan ve enerji gerektiren aksonal taşınmadan sorumlu elemanlardır. Hacimce oldukça büyük olan nöronlar için aksonal taşınma kritik bir olaydır ve hücre içi homoestazisinin devam ettirilebilmesi için zorunludur. Taşınma anında aksaklık gelişmesi, aksonal taşınma elemanlarını kodlayan genlerde mutasyonların meydana gelmesi, enerji üretimi veya kullanımında sorun meydana gelmesi gibi durumlar hücre içi iletimin engellenmesine, hücreler arası iletişimin bozulmasına ve nöronal apoptoza sebep olabilmektedir. Geri dönüşü olmayan ve ilerleyici nöron kayıpları ise nörodejenerasyonla sonuçlanarak nörodejeneratif hastalıkların ortaya çıkmasına neden olabilmektedir.

Keywords

Nörodejeneratif hastalıklar, aksonal taşınma, motor protein, kinesin, dinein

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