Title:Tau Truncation is a Productive Posttranslational Modification of Neurofibrillary Degeneration in Alzheimer’s Disease
Volume: 7
Issue: 8
Author(s): B. Kovacech and M. Novak
Affiliation:
Keywords:
Tau truncation; Alzheimer’s disease; neurofibrillary degeneration; tau transition.
Abstract: Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer’s disease
(AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein
tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD,
most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for
the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the
human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the
progression of the disease. In addition, western blot analyses of tau species in AD brains reveal multitudes of various
truncated forms. In this review we summarize evidence showing that tau truncation alone is sufficient to induce the complete
cascade of neurofibrillary pathology, including hyperphosphorylation and accumulation of misfolded insoluble
forms of tau. Therefore, proteolytical abnormalities in the stressed neurons and production of aberrant tau cleavage products
deserve closer attention and should be considered as early therapeutic targets for Alzheimer’s disease.
