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A biophysical perspective on the unexplored mechanisms driving Parkinson’s disease by amphetamine-like stimulants

Neural Regeneration Research 2021年第11期16卷 2213-2214页

作者： Carla Ferreira joana couceiro Sandra Tenreiro Alexandre Quintas Molecular Pathology and Forensic Biochemistry Laboratory Centro de Investigação Interdisciplinar Egas MonizP-2825-084 CaparicaPortugal Laboratório de Ciências Forenses e Psicológicas Egas Moniz Campus Universitário–Quinta da GranjaMonte de CaparicaP-2825-084 CaparicaPortugal Faculty of Medicine of Porto University Al.Prof.Hernâni MonteiroP-4200–319 PortoPortugal iNOVA4Health CEDOCNOVA Medical SchoolNMSUniversidade Nova de Lisboa1169-056 LisboaPortugal

Epidemiological studies have reported an increased risk of Parkinson’s disease(PD)development in amphetamine-type stimulant users during their lifetime(Garwood et al.,2006;Rumpf et al.,2017).Protein inclusions mainly composed of misfolded and aggregatedα-synuclein are the pathological hallmark of PD and other disorders known as synucleinopathies.Molecular studies present evidence that amphetamine upregulatesα-synuclein synthesis in substantia nigra.The increment ofα-synuclein levels promotes its aggregation and amyloid fibril formation,increasing reactive oxygen species(ROS),and consequently dopamine oxidation(Wang and Witt,2014),known to be toxic for dopaminergic neurons involved in motor function and limbicmotor integration.Over the years,these damaged cells lose their functionality and may die precociously,depleting the reserve of neural cells necessary for the normal neurological function which contributes to the onset of PD,when a critical number of cells are lost(Garwood et al.,2006).Therefore,the use of amphetamine-type stimulants may be a trigger event in the development of PD and parkinsonism,in conjugation to other risk factors that a given individual may hold.Despite the evidence,a previous study suggests that there is not enough data to corroborate the loss of dopamine neurons due to human amphetamine-type stimulant exposure,and consequently its implication in the PD development(Kish et al.,2017).

关键词： driving increment lifetime

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