Aberrant aggregation of ␣-synuclein (␣-syn) to form fibrils and insoluble aggregates has been implicated in the pathogenic processes of many neurodegenerative diseases. Despite the dramatic effects of dopamine in inhibiting the formation of ␣-syn fibrils by stabilization of oligomeric intermediates in cell-free systems, no studies have examined the effects of intracellular dopamine on ␣-syn aggregation. To study this process and its association with neurodegeneration, intracellular catechol levels were increased to various levels by expressing different forms of tyrosine hydroxylase, in cells induced to form ␣-syn aggregates. The increase in the steady-state dopamine levels inhibited the formation of ␣-syn aggregates and induced the formation of innocuous oligomeric intermediates. Analysis of transgenic mice expressing the disease-associated A53T mutant ␣-syn revealed the presence of oligomeric ␣-syn in nondegenerating dopaminergic neurons that do contain insoluble ␣-syn. These data indicate that intraneuronal dopamine levels can be a major modulator of ␣-syn aggregation and inclusion formation, with important implications on the selective degeneration of these neurons in Parkinson's disease.
Adjuvant gemcitabine plus S-1 chemotherapy may be one of several factors contributing to improved outcomes after aggressive surgical resection of advanced biliary carcinoma in recent years.
Postoperative CA19-9 level is a better prognostic factor than preoperative CA19-9 level, and curative surgery for resectable pancreatic cancer should be tried regardless of the preoperative CA19-9 level.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.