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

• Main Authors: Mujtaba Aamir Bhat, Khurshid Ahmad, Mohd Sajjad Ahmad Khan, Mudasir Ahmad Bhat, Ahmad Almatroudi, Safikur Rahman, Arif Tasleem Jan
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Biomolecules
• Subjects: aggregation; neurodegenerative diseases; osmolytes; protein folding; therapeutics; unfolded protein response
• Online Access: https://www.mdpi.com/2218-273X/10/6/863

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.