Pranshul Sethi¹, Ronald Darwin. C², Ramakrishna Borra³, Shahin Vahora⁴, Ankur Vashi⁵, Rajesh Kumar Mukherjee⁶,

Belide Pavani⁷, Gaurav Tiwari^8*

¹Department of Pharmacology, College of Pharmacy, Shri Venkateshwara University affiliation, Gajraula, India

²Department of Pharmacology, School of Pharmaceutical Sciences, Vels Institute of Science Technology & Advanced Studies, Chennai - 600 117, India

³Research and Development, American Regent, 6610 New Albany, OH 43054, USA

⁴Navinta LLC, 1499 lower ferry road, Ewing, NJ, USA - 08618

⁵Flamma USA, 383 Phoenixville Pike-Malvern,PA 19355-  USA

⁶Brainware University, Department of Pharmaceutical Technology, 398, Ramkrishnapur Rd, near Jagadighata Market, Barasat, Kolkata, West Bengal 700125, India

⁷CMR college of pharmacy, Kandlakoya (V), Medchal, Medchal Road, Hyderabad 501401, India

⁸PSIT-Pranveer Singh Institute of Technology (Pharmacy), Kalpi Road, Bhauti, Kanpur-208020, India

* Address    for  Correspondence:

Professor Gaurav Tiwari

Email: drgauravtiwari81@gmail.com

Phone: +91-8299179267

Abstract

Abnormal hyperphosphorylation and microtubule-associated protein tau aggregation development in the brain are characteristics of neurodegenerative diseases referred to as tauopathies, which include Alzheimer's disease (AD).  The current review summarizes the complex relationships that exist between oxidative stress and tau illness, with particular attention to the roles played by the tau protein, reactive oxygen species and their consequences, and tau phosphorylation and oxidative stress. Two key elements of detrimental cycle that are critical in neurodegenerative tauopathies are tau hyperphosphorylation and oxidative stress. When tau and microtubules are not connected properly, microtubule instability, issues with microtubule transport, and ultimately neuronal death result. While the causes of the more prevalent sporadic late-onset variants and the connections between tau hyperphosphorylation and neurodegeneration remain largely unknown, mutations in the microtubule-associated protein tau (MAPT) gene have been identified in familial cases of early-onset tauopathies. Another detrimental feature of tauopathies is oxidative stress, but the exact role it plays in the development of the disease is unclear. The source of reactive oxygen species (ROS), which lead to oxidative stress within neural tissue, remains an unresolved topic. Although mitochondria have historically been thought to be a primary source of oxidative stress, microglial cells have recently been discovered to create reactive oxygen species in tauopathies. In conclusion, enhancing our comprehension of the impact of oxidative stress on various diseases could facilitate the identification of new disease markers and lead to the formulation of treatment strategies aimed at halting, reversing, or mitigating disease progression.

Keywords  Alzheimer's disease, Tau hyperphosphorylation, Oxidative stress, Mitochondrial dysfunction, Neurodegenerative tauopathies

PDF  Mechanistic Insights into Tau Protein-Mediated Regulation of Oxidative Stress.pdf