The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know
نویسندگان
چکیده
3,4-Dihydroxyphenylacetaldehyde (DOPAL) is the focus of catecholaldehyde hypothesis for pathogenesis Parkinson’s disease and other Lewy body diseases. The produced via oxidative deamination catalyzed by monoamine oxidase (MAO) acting on cytoplasmic dopamine. DOPAL autotoxic, in that it can harm same cells which produced. Normally, detoxified aldehyde dehydrogenase (ALDH)-mediated conversion to 3,4-dihydroxyphenylacetic acid (DOPAC), rapidly exits neurons. Genetic, environmental, or drug-induced manipulations ALDH build up promote catecholaminergic neurodegeneration. A concept derived from imputes deleterious interactions between protein alpha-synuclein (αS), a major component bodies. potently oligomerizes αS, αS oligomers impede vesicular mitochondrial functions, shifting fate dopamine toward MAO-catalyzed formation DOPAL—destabilizing vicious cycles. Direct indirect effects DOPAL-induced misfolded proteins could “freeze” intraneuronal reactions, plasticity required neuronal homeostasis. extent toxicity mediated with vice versa, poorly understood. Because numerous secondary such as augmented spontaneous oxidation MAO inhibition, there has been insufficient testing animal models. clinical pathophysiological significance genetics, emotional stress, environmental agents, relevant are matters future research. imposing complexity catecholamine metabolism seems require computational modeling approach elucidate pathogenetic mechanisms devise pathophysiology-based, individualized treatments.
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ژورنال
عنوان ژورنال: International Journal of Molecular Sciences
سال: 2021
ISSN: ['1661-6596', '1422-0067']
DOI: https://doi.org/10.3390/ijms22115999