Tau Abnormalities and the Potential Therapy in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that is characterized by progressive memory loss and two main pathological hallmarks, including the extracellular amyloid plaques and intracellular neurofibrillary tangles. The microtubule-related protein tau is involved in the pathogenesis of many neurological diseases commonly known as tauopathies and is found to be abnormally hyperphosphorylated in AD and accumulated in neurons. Besides hyperphosphorylation, tau also undergoes abnormal glycosylation, ubiquitination, glycation, and other posttranslational modifications. These abnormalities lead to the aberrant aggregation of tau in the synaptic loci in AD. In this review, we highlighted the most recent studies about how tau is abnormally regulated and how those abnormalities play important roles in the pathogenesis of AD.

Potential Bidirectional Relationship Between Periodontitis and Alzheimer’s Disease

“…The tau protein structure is composed of four main regions: an acidic N-terminal (NT); a proline-rich region responsible for the binding to microtubules; four repeat domains (R1-4), also called microtubule-binding domains (MBDs) (Drewes et al, 1995;Sengupta et al, 1998;Gendron and Petrucelli, 2009); and a C-terminal (CT) region. Importantly, tau activity can be modulated by a wealth of posttranslational modifications (PTMs), such as acetylation, glycosylation, glycation, methylation, truncation, nitration, ubiquitination, and phosphorylation (Almansoub et al, 2019). However, phosphorylation is the most commonly described and investigated since it is centrally involved in the formation of pathologic aggregates.…”

“…However, phosphorylation is the most commonly described and investigated since it is centrally involved in the formation of pathologic aggregates. Indeed, the aggregation of tau has been correlated to a broad spectrum of neurological diseases, including AD, known as "tauopathies" (Congdon and Sigurdsson, 2018;Almansoub et al, 2019). This PTM is physiologically regulated by the balance between tau kinases and phosphatase activities (Martin et al, 2013).…”

Oligomerization and Conformational Change Turn Monomeric β-Amyloid and Tau Proteins Toxic: Their Role in Alzheimer’s Pathogenesis

“…The repeat regions (together with short joining sequences) are the microtubule binding domain of tau. N-terminal truncation occurs at early stage of AD and provides a toxic 20-22 kDa tau fragment [142].…”

“…Tau proteins show a large number of post-translational modifications (PTMs) [142] (see Figure 5). PTMs may occur under both physiological and pathophysiological conditions.…”

Preventive Electroacupuncture Ameliorates D‐Galactose‐Induced Alzheimer’s Disease‐Like Pathology and Memory Deficits Probably via Inhibition of GSK3β/mTOR Signaling Pathway

“…Intracellular NFTs accumulation as a result of tau hyperphosphorylation and aggregation is the early pathology in AD [10], and NFTs deposition can even be found in aging brains without obvious memory deficits [11]. erefore, prevention of neurofibrillary tangles accumulation as a result of tau hyperphosphorylation [49] and autophagy degradation deficits [50] may be a promising efficient intervention strategy for AD. In the present study, we investigated whether preventive EA treatment during aging could attenuate memory deficits in consequence of tau hyperphosphorylation.…”