Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases

Biomolecules

MohdSajjad Ahmad Khan¹  Khurshid Ahmad²  Ahmad Almatroudi³  Safikur Rahman⁴  MujtabaAamir Bhat⁵  MudasirAhmad Bhat⁵  ArifTasleem Jan⁵ 

[1]Department of Basic Sciences, Imam Abdulrahman Bin Faisal University, Dammam 31451, Saudi Arabia

[2]Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea

[3]Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia

[4]Munshi Singh College, BR Ambedkar Bihar University, Muzaffarpur, Bihar 845401, India

[5]School of Biosciences and Biotechnology, Baba Ghulam Shah Badshah University, Rajouri 185234, India

关键词: aggregation;    neurodegenerative diseases;    osmolytes;    protein folding;    therapeutics;    unfolded protein response;   

DOI  :  10.3390/biom10060863

来源: DOAJ

【 摘 要 】

Neurodegenerative diseases (NDs) are characterized by the accumulation of misfolded proteins. The hallmarks of protein aggregation in NDs proceed with impairment in the mitochondrial function, besides causing an enhancement in endoplasmic reticulum (ER) stress, neuroinflammation and synaptic loss. As accumulation of misfolded proteins hampers normal neuronal functions, it triggers ER stress, which leads to the activation of downstream effectors formulating events along the signaling cascade—referred to as unfolded protein response (UPRER) —thereby controlling cellular gene expression. The absence of disease-modifying therapeutic targets in different NDs, and the exponential increase in the number of cases, makes it critical to explore new approaches to treating these devastating diseases. In one such approach, osmolytes (low molecular weight substances), such as taurine have been found to promote protein folding under stress conditions, thereby averting aggregation of the misfolded proteins. Maintaining the structural integrity of the protein, taurine-mediated resumption of protein folding prompts a shift in folding homeostasis more towards functionality than towards aggregation and degradation. Together, taurine enacts protection in NDs by causing misfolded proteins to refold, so as to regain their stability and functionality. The present study provides recent and useful insights into understanding the progression of NDs, besides summarizing the genetics of NDs in correlation with mitochondrial dysfunction, ER stress, neuroinflammation and synaptic loss. It also highlights the structural and functional aspects of taurine in imparting protection against the aggregation/misfolding of proteins, thereby shifting the focus more towards the development of effective therapeutic modules that could avert the development of NDs.

【 授权许可】

Unknown