Neurodegenerative diseases like Alzheimer's, Parkinson's and
Huntington's disease involves abnormal aggregation and accumulation of toxic
proteins aggregates. Post-translational modifications (PTMs) of the causative
proteins play an important role in the etiology of disease as they could either slow down or accelerate the
disease progression.
Alzheimer disease is associated with the aggregation and accumulation of two major
protein aggregates-intracellular neurofibrillary tangles made up of
microtubule-associated protein Tau and extracellular
Amyloid-β plaques. Post-translational modifications are important for the regulation of Tau`s function but an imbalance in PTMs may lead to abnormal Tau function and aggregation. Tau methylation is one of the important PTM of Tau in its physiological state. However, the methylation signature on Tau
lysine changes once it acquires pathological aggregated form. Tau methylation can compete with other PTMs such as acetylation and ubiquitination. The state of PTM at these sites determines the fate of
Tau protein in terms of its function and stability. The global methylation in neurons, microglia and astrocytes are involved in multiple cellular functions involving their role in epigenetic regulation of gene expression via DNA methylation. Here, we have discussed the effect of methylation on Tau function in a site-specific manner and their cross-talk with other
lysine modifications. We have also elaborated the role of methylation in epigenetic aspects and neurodegenerative conditions associated with the imbalance in methylation metabolism affecting global methylation state of cells. Video abstract.