Nature of Tau-Associated Neurodegeneration and the Molecular Mechanisms

Abstract

Neurodegeneration is defined as the progressive loss of structure or function of the neurons. As the nature of degenerative cell loss is currently not clear, there is no specific molecular marker to measure neurodegeneration. Therefore, researchers have been using apoptotic markers to measure neurodegeneration. However, neurodegeneration is completely different from apoptosis by morphology and time course. Lacking specific molecular marker has been the major hindrance in research of neurodegenerative disorders. Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and tau accumulation forming neurofibrillary tangles is a hallmark pathology in the AD brains, suggesting that tau must play a critical role in AD neurodegeneration. Here we review part of our published papers on tau-related studies, and share our thoughts on the nature of tau-associated neurodegeneration in AD.

Current understanding of metal ions in the pathogenesis of Alzheimer’s disease

“…[5][6][7]. Recent studies suggest that tau hyperphosphorylation may play a dual role in AD neurodegeneration, i.e., tau hyperphosphorylation renders the cells more resistant to acute apoptosis [8][9][10][11][12], while the increasing intracellular tau accumulation induces multiple cellular impairments, including endoplasmic reticulum (ER) stress, deficits of mitophagy and autophagy, deficits of synaptic transmission, etc., and eventually leads to a chronic neurodegeneration [5,13,14].…”

Neurorestorative Mulberries Potential of Alzheimer’s Disease in Animal Model

“…stress in rats' brain and by inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase, the key enzymes linked to AD [1,2]. Other classes of polyphenols including anthocyanins, flavanols, flavones, triterpenes, and stilbenes are found in Morus species in appropriate amount.…”

“…Other classes of polyphenols including anthocyanins, flavanols, flavones, triterpenes, and stilbenes are found in Morus species in appropriate amount. The potential effects of compounds related to these classes in reducing cerebral injury and improving cognitive function were reported [1,2,6]. Morus species has been approved as effective against metabolic deteriorations and Al-induced developmental retinopathy [5,9].…”

“…Alzheimer's disease (AD) continues to be a growing health concern worldwide as it is considered one of the most chronic neurodegenerative diseases [1]. It is characterized by progressive and slow neurodegeneration in different regions of brain [2]. Aluminum (Al) is a neurotoxin that suppresses many of the biological functions in humans and animals causing various adverse effects [3].…”

“…On exposure to Al, the relationship between amyotrophic lateral sclerosis and dialysis encephalopathy in the neurodegenerative disorders as Alzheimer has been suggested [3]. Abnormal levels of oxidative stress have been reported in an AD in bloodstream and brain [1,2]. Biomarkers of oxidative stress in AD are classified as an oxidative attack on proteins leads to the formation of protein carbonyls (PCs) and protein nitration as well as superoxide dismutase (SOD) and lipid peroxidation [4].…”