Mitochondria: key players in the neurotoxic effects of amphetamines

• Type: Another Publication in an International Scientific Journal
• Date: 2015

Authors

Barbosa, DJ (Author) Other; Capela, JP (Author) Other; Feio Azevedo, R (Author) Other; Teixeira Gomes, A (Author) Other; Bastos, ML (Author) FFUP; Carvalho, F (Author) FFUP

Journal

Title: Archives of Toxicology

Vol. 89

Pages: 1695-1725

ISSN: 0340-5761

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00G-1WG

DOI: 10.1007/s00204-015-1478-9

Abstract (EN): Amphetamines are a class of psychotropic drugs with high abuse potential, as a result of their stimulant, euphoric, emphathogenic, entactogenic, and hallucinogenic properties. Although most amphetamines are synthetic drugs, of which methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine ("ecstasy") represent well-recognized examples, the use of natural related compounds, namely cathinone and ephedrine, has been part of the history of humankind for thousands of years. Resulting from their amphiphilic nature, these drugs can easily cross the blood-brain barrier and elicit their well-known psychotropic effects. In the field of amphetamines' research, there is a general consensus that mitochondrial-dependent pathways can provide a major understanding concerning pathological processes underlying the neurotoxicity of these drugs. These events include alterations on tricarboxylic acid cycle's enzymes functioning, inhibition of mitochondrial electron transport chain's complexes, perturbations of mitochondrial clearance mechanisms, interference with mitochondrial dynamics, as well as oxidative modifications in mitochondrial macromolecules. Additionally, other studies indicate that amphetamines-induced neuronal toxicity is closely regulated by B cell lymphoma 2 superfamily of proteins with consequent activation of caspase-mediated downstream cell death pathway. Understanding the molecular mechanisms at mitochondrial level involved in amphetamines' neurotoxicity can help in defining target pathways or molecules mediating these effects, as well as in developing putative therapeutic approaches to prevent or treat the acute- or long-lasting neuropsychiatric complications seen in human abusers.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 31