Tau Pathology in Parkinson's Disease

Abstract

Tau protein-a member of the microtubule-associated protein family-is a key protein involved in many neurodegenerative diseases. Tau pathology in neurodegenerative diseases is characterized by pathological tau aggregation in neurofibrillary tangles (NFTs). Diseases with this typical pathological feature are called tauopathies. Parkinson's disease (PD) was not initially considered to be a typical tauopathy. However, recent studies have demonstrated increasing evidence of tau pathology in PD. A genome-wide association (GWA) study indicated a potential association between tauopathy and sporadic PD. The aggregation and deposition of tau were also observed in ~50% of PD brains, and it seems to be transported from neuron to neuron. The aggregation of NFTs, the abnormal hyperphosphorylation of tau protein, and the interaction between tau and alpha-synuclein may all contribute to the cell death and poor axonal transport observed in PD and Parkinsonism.

Keywords: Parkinson's disease (PD); alpha-synuclien; hyperphosphorylation; tau protein; tauopathy.

Figure 1

Tauopathy in PD. Tau proteins are integrated with microtubules and stabilize microtubules in physiological condition. However, when tau proteins are hyperphosphorylated, they begin to disintegrate from microtubules, causing neuronal dysfunction. Hyperphosphorylated tau proteins prone to assemble together to form oligomers and develop into filamentous neurofibrillary tangles (NFTs). Hyperphosphorylated tau proteins also interact with α-synuclein to promote aggregation and fibrilization each other, and subsequently cause the formation of lewy bodies and axonal transport dysfunction.