Microtubule acetylation dyshomeostasis in Parkinson’s disease

作     者：Padmashri Naren Khan Sabiya Samim Kamatham Pushpa Tryphena Lalitkumar K.Vora Saurabh Srivastava Dharmendra Kumar Khatri Shashi Bala Singh 

作者机构：Molecular and Cellular Neuroscience LabDepartment of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and Research(NIPER)HyderabadTelangana 500037India School of PharmacyQueen’s University Belfast97 Lisburn RoadBelfast BT97BLUK Department of PharmaceuticsNational Institute of Pharmaceutical Education and Research(NIPER)HyderabadTelangana 500037India 

出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)

年 卷 期：2023年第12卷第1期

页      面：576-600页

核心收录：

学科分类：0710[理学-生物学] 0402[教育学-心理学(可授教育学、理学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1010[医学-医学技术（可授医学、理学学位）] 1009[医学-特种医学] 10[医学] 

基　　金：Department of Pharmaceuticals Ministry of Chemicals and Fertilizers NIPER-Hyderabad 

主　　题：Parkinson’s disease Microtubule acetylation Tubulin PTMs Mitochondria Axonal transport HDAC6 SIRT2 inhibitors 

摘      要：The inter-neuronal communication occurring in extensively branched neuronal cells is achieved primarily through the microtubule(MT)-mediated axonal transport *** mechanistically regulated system delivers cargos(proteins,mRNAs and organelles such as mitochondria)back and forth from the soma to the *** proteins like kinesins and dynein mechanistically regulate polarized anterograde(from the soma to the synapse)and retrograde(from the synapse to the soma)commute of the cargos,*** axonal transport of such cargos is achieved by altering the microtubule stability via post-translational modifications(PTMs)ofα-andβ-tubulin heterodimers,core components constructing the *** within the lumen of MTs,K40 acetylation ofα-tubulin viaα-tubulin acetyl transferase and its subsequent deacetylation by HDAC6 and SIRT2 are widely scrutinized PTMs that make the MTs highly flexible,which in turn promotes their *** movement of various motor proteins,including kinesin-1(responsible for axonal mitochondrial commute),is enhanced by this PTM,and dyshomeostasis of neuronal MT acetylation has been observed in a variety of neurodegenerative conditions,including Alzheimer’s disease and Parkinson’s disease(PD).PD is the second most common neurodegenerative condition and is closely associated with impaired MT dynamics and deregulated tubulin acetylation *** the relationship between status of MT acetylation and progression of PD pathogenesis has become a chicken-and-egg question,our review aims to provide insights into the MT-mediated axonal commute of mitochondria and dyshomeostasis of MT acetylation in *** enzymatic regulators of MT acetylation along with their synthetic modulators have also been briefly *** towards a tubulin-based therapy that enhances MT acetylation could serve as a disease-modifying treatment in neurological conditions that lack it.