Alpha-tubulin deacetylase as a potential and novel target for the prevention of Parkinson's disease progression

摘要

Parkinson's disease(PD)is the second most common neurodegenerative disorder and is characterized by its progressive course.The current therapies are aimed at alleviating symptoms by rescuing the unbalanced physiological dopamine metabolism and recovery of damaged neuronal circuits.However,these strategies result in insufficient clinical benefits for many patients and fail to halt disease progression.Therefore,new therapeutic targets could serve as the gateway against PD degeneration.One pathological hallmark of PD is the formation of intracytoplasmic protein inclusions or Lewy bodies,in neurons.Recent studies have suggested that Lewy bodies are formed similarly to aggresomes,and results have supported the concept that the novel cellular organelle,the aggresome,is a cytoprotective response that sequesters and facilitates clearance of potentially toxic protein aggregates.In addition,α-tubulin deacetylase has been shown to regulate aggresome formation and rescue neural cell viability in response to misfolded protein.Therefore,the regulation of aggresome formation to trigger cellular self-protection system could arrest PD progression.The present study discusses research progress related to Lewy bodies,aggresomes,and histone deacetylases,with an emphasis on histone deacetylase 6 and sirtuin type 2.