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Alpha‐synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells
Author(s) -
Tehranian Roya,
Montoya Susana E.,
Van Laar Amber D.,
Hastings Teresa G.,
Perez Ruth G.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04146.x
Subject(s) - dopamine , dopaminergic , tyrosine hydroxylase , aromatic l amino acid decarboxylase , dopamine transporter , tyrosine , alpha synuclein , catecholamine , biology , striatum , biochemistry , chemistry , medicine , endocrinology , parkinson's disease , disease
Alpha‐synuclein is a presynaptic protein strongly implicated in Parkinson's disease (PD). Because dopamine neurons are invariably compromised during pathogenesis in PD, we have been exploring the functions of alpha‐synuclein with particular relevance to dopaminergic neuronal cells. We previously discovered reduced tyrosine hydroxylase (TH) activity and minimal dopamine synthesis in stably‐transfected MN9D cells overexpressing either wild‐type or A53T mutant (alanine to threonine at amino acid 53) alpha‐synuclein. TH, the rate‐limiting enzyme in dopamine synthesis, converts tyrosine to l ‐dihydroxyphenylalanine (L‐DOPA), which is then converted to dopamine by the enzyme, aromatic amino acid decarboxylase (AADC). We confirmed an interaction between alpha‐synuclein and AADC in striatum. We then sought to determine whether wild‐type or A53T mutant alpha‐synuclein might have affected AADC activity in dopaminergic cells. Using HPLC with electrochemical detection, we measured dopamine and related catechols after L‐DOPA treatments to bypass the TH step. We discovered that while alpha‐synuclein did not reduce AADC protein levels, it significantly reduced AADC activity and phosphorylation in our cells. These novel findings further support a role for alpha‐synuclein in dopamine homeostasis and may explain, at least in part, the selective vulnerability of dopamine neurons that occurs in PD.