Autophagy as a gateway for the effects of methamphetamine: From neurotransmitter release and synaptic plasticity to psychiatric and neurodegenerative disorders. (September 2021)

• Record Type: Journal Article
• Authors: Limanaqi, Fiona; Busceti, Carla L.; Celli, Roberta; Biagioni, Francesca; Fornai, Francesco
• Is Part Of: Progress in neurobiology. Volume 204(2021)
• Publication Date: 2021-09
• Subjects: AADC aromatic amino acid decarboxylase -- AD aldehyde dehydrogenase -- AGE advanced glycation end-product -- AMPAR α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor -- AMPK 5′ AMP-activated protein kinase -- Atg autophagy-related gene -- BBB blood-brain barrier -- BECN1 beclin 1 -- cAMP cyclic adenosine monophosphate -- CDK5 cyclin-dependent kinase 5 -- CMA chaperone-mediated autophagy -- CNS central nervous system -- CREB cAMP response element binding protein -- CRMP2 collapsin response mediator protein-2 -- DA dopamine -- DAMPs damage-associated molecular patterns -- DAT dopamine transporter -- DISC1 disrupted in schizophrenia 1 -- DOPAC 3, 4-dihydroxyphenylacetic acid -- DOPALD 3, 4-dihydroxyphenylacetaldehyde -- DPYSL2 dihydropyrimidinase-like 2 -- DRD1 type 1-dopamine receptor -- DRD2 type 2-dopamine receptor -- DβH dopamine β hydroxylase -- FOXO3 transcription factor forkhead box O3 -- GABA gamma-aminobutyric acid -- GFAP glial fibrillary acidic protein -- GLUT glutamate -- GSK3-β glycogen synthase kinase beta -- HD Huntington's disease -- HMGB1 high-mobility group box-1 -- Hsc70 heat shock cognate 71 kDa protein -- ICAM-1 cellular adhesion molecule -- IL-1β interleukin 1β -- IL-6 interleukin 6 -- MAO monoamine-oxidase -- MAPK mitogen-activated protein kinase -- MCP-1 monocyte chemo-attractant protein 1 -- METH methamphetamine -- MIC microautophagy -- MMP-9 matrix metalloproteinase-9 -- MUD methamphetamine use disorder -- MSNs medium-sized spiny neurons -- mTOR mammalian/mechanistic target of rapamycin -- NE norepinephrine -- NF-κB nuclear factor-kappa B -- NLRP3 Nod-like Receptor Protein 3 -- NMDAR N-Methyl-d-aspartate receptor -- NOX2 NAD(P)H oxidase 2 -- NRF-2 nuclear factor erythroid 2 (NFE2)-related factor 2 -- PD Parkinson's disease -- PGC-1α peroxisome proliferator-activated receptor gamma coactivator 1-alpha -- PI3P phosphatidylinositol 3-phosphate -- PKC protein kinase c -- RAGE receptor for advanced glycation end-product -- RVLM rostral ventrolateral medulla -- SNpc substantia nigra pars compacta -- TFAM mitochondrial transcription factor A -- TFEB transcription factor EB -- TH tyrosine hydroxylase -- TLR toll-like receptor -- TNF-α tumor necrosis factor-α -- UPS ubiquitin-proteasome system -- VCAM-1 vascular cell adhesion molecule 1 -- VMAT-1/2 vesicular monoamine transporter type-1/2 -- VPS34 vacuolar protein sorting 34 -- VPS35 vacuolar protein sorting 35 -- VTA ventral tegmental area -- 5-HT 5-hydroxytryptamine, serotonin; Dopamine -- Addiction -- Psychosis -- Parkinsonism -- LC3 -- mTOR -- GSK3-β -- PKC -- CDK5; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2021.102112
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: Autophagy modulates neurotransmitter release, synaptic plasticity, and neuronal survival. METH impairs the autophagy machinery by altering LC3 compartmentalization. Autophagy impairment fosters abnormal DA transmission and proteinopathy. METH-induced autophagy impairment fosters maladaptive plasticity and neurotoxicity. Autophagy bridges drug abuse, psychiatric manifestations, and neurodegenerative phenomena. Abstract: As a major eukaryotic cell clearing machinery, autophagy grants cell proteostasis, which is key for neurotransmitter release, synaptic plasticity, and neuronal survival. In line with this, besides neuropathological events, autophagy dysfunctions are bound to synaptic alterations that occur in mental disorders, and early on, in neurodegenerative diseases. This is also the case of methamphetamine (METH) abuse, which leads to psychiatric disturbances and neurotoxicity. While consistently altering the autophagy machinery, METH produces behavioral and neurotoxic effects through molecular and biochemical events that can be recapitulated by autophagy blockade. These consist of altered physiological dopamine (DA) release, abnormal stimulation of DA and glutamate receptors, as well as oxidative, excitotoxic, and neuroinflammatory events. Recent molecular insights suggest that METH early impairs the autophagy machinery, though its functional significance remains to be investigated. Here we discuss evidence suggesting that alterations of DA transmission and autophagy are intermingled within a chain of events underlying behavioral alterations and neurodegenerative phenomena produced by METH. Understanding how METH alters the autophagy machinery is expected to provide novel insights into the neurobiology of METH addiction sharing some features with psychiatric disorders and parkinsonism.