Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

Parkinson disease (PD) is the second most common multisystem neurodegenerative disease after Alzheimer disease, whose incidence rates are around 1% and 4% of the population above the age of 60 and 80 years, respectively. It is a progressive movement disorder, which is clinically manifested by resting tremor, rigidity, postural instability and akinesia/bradykinesia usually along with cognitive impairment. The major hallmarks of PD are the loss of dopaminergic neurons and formation of Lewy Bodies (LBs) in the substantia nigra pars compacta (SNpc). The dopamine(DA) replacement therapy with levodopa(LDOPA) is a milestone in the treatment of PD. However, L-DOPA can induce motor fluctuation and dyskinesias after several years of treatment. So it is of important realistic significance to explore effective approaches for prevention, diagnosis and treatment of PD through clarifying its pathological mechanism.

Catechol Tetrahydroisoquinolines
Catechol Tetrahydroisoquinolines

a-syn was the first reported gene, the mutation of which was described in a family with dominantly inherited PD in 1997. a-syn was believed as the key protein involved in PD, overexpression of which has been wildly used as PD models. Although increasing studies on the physiological and pathological roles of a-syn popped up in recent years, the exact mechanism of a-syn aggregation in PD is still elusive.


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