Parkin and Other Proteins of Parkinson's Disease

摘要

Parkinson's disease (PD) is one of the most common degenerative diseases of the central nervous system (CNS) and affects nearly 2% of the population over the age of 65 and 5% over the age of 85. Moreover, the recent estimates indicate that a number of PD sufferers will increase in time, which is associated with population ageing phenomenon. The pathogenesis of PD is still not fully understood. It has been found that pathogenesis of this disease may be mediated by proteins, such as alpha-synuclein (ASN), Parkin, leucine-rich repeat kinase-2 (LRRK2) and high temperature requirement protein (HTRA2) and others e.g., protein deglycase (DJ-1) and PTEN-induced putative kinase 1 (PINK1), and TMEM230. Physiologically ASN may modulate catecholamine biosynthesis, by downregulating the expression of tyrosine hydroxylase as well as genes involved in the dopamine (DA) synthesis. Furthermore, structural and functional disorders of the ASN are observed in several neurodegenerative diseases, including PD. LRRK2 is associated with membrane structures including the outer membrane of mitochondria and synaptic vesicles. It is also involved in vesicular transport and turnover of cellular proteins, as well as the proper functioning of the mitochondria. The overexpression of LRRK2 alone or along with ASN may increase the destructive processes in the PD. Furthermore, dysfunction of mitochondria is also responsible for the changes in the structure of other proteins such as HTRA2 and Parkin. Parkin may affect the activity of mitochondrial complex, and indirectly may alter the level of oxidative stress. It is believed that Parkin rather protects mtDNA from damage in the oxidative stress conditions and even induces repair mechanism. Moreover, in neurons Parkin may interact with the DA thus contributing to ASN aggregation. Understanding the interactions of proteins involved in the pathogenesis of PD may contribute to a better knowledge of the causes of disease and early diagnosis and the effective treatment of this disease.