Autophagy in neuroinflammatory diseases

• Published in: Autoimmunity reviews Vol. 16; no. 8; pp. 856 - 874
• Main Authors: Muller, Sylviane, Brun, Susana, René, Frédérique, de Sèze, Jérôme, Loeffler, Jean-Philippe, Jeltsch-David, Hélène
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2017; Elsevier
• Subjects: Allergy and Immunology; Amyotrophic lateral sclerosis; Animals; Autophagy; Central Nervous System Diseases - immunology; Chronic inflammatory demyelinating polyradiculoneuropathy; CMA-mediated autophagy; Humans; Inflammation - immunology; Life Sciences; Neurodegenerative Diseases - immunology; Neuropsychiatric lupus; Peptide Fragments - immunology; Peripheral Nervous System Diseases - immunology; Therapeutic peptide; APP; TREM; BBB; Parkinson's disease; chronic inflammatory demyelinating polyradiculoneuropathy; mutated Htt; ALS; neuropsychiatric systemic lupus erythematosus; CMA-mediated autophagy; MHC; mHtt; major histocompatibility complex; amyotrophic lateral sclerosis; SLE; Aβ; SQSTM1/p62; experimental autoimmune encephalomyelitis; lysosome-associated membrane protein 2A; CMA; autophagy-related; mTOR; UPS; lymphoproliferation; Alzheimer's disease; α-synuclein; Toll-like receptor; unc-51 like autophagy activating kinase-1; chaperone-mediated autophagy; antibody; AD; IL; T cell receptor; transactive response DNA binding protein 43 kDa; MS; heat shock 70-kDa protein 8; amyloid-β; EAE; ER; superoxide dismutase-1; blood brain barrier; EAN; TDP-43; NMDAR; Bcl-2 interacting myosin/moesin-like coiled-coil protein-1; microtubule-associated protein 1 light chain 3β; Ab; HSPA8/HSC70; ATG6/Beclin-1; NP; TCR; antigen-presenting cell; triggering receptors expressed on myeloid cells; MRL; neuropsychiatric; phosphatidylinositol triphosphate kinase complex 3; Htt; experimental autoimmune neuritis; LAMP2A; MAP1LC3B/LC3; ATG18/WIPI; mammalian target of rapamycin; systemic lupus erythematosus; amyloid precursor protein; huntingtin; TLR; interleukin; Therapeutic peptide; WD-repeat protein interacting with phosphoinositides; SNCA; phosphatase and tensin homolog (PTEN)-induced putative kinase 1; PI3KC3; Murphy Roths large; OS; sequestosome-1/ubiquitin-binding protein p62; multiple sclerosis; PtdIns3/PI3P; ATG1/ULK; Huntington's disease; CIDP; N-methyl- d-aspartate receptor; lpr; SOD1; ubiquitin-proteasome system; phosphatidylethanolamine; phosphatidylinositol-3-phosphate; APC; ATG; PD; PE; NPSLE; HD; Neuropsychiatric lupus; endoplasmic reticulum; oxidative stress; PINK1/PARK6; Chronic inflammatory demyelinating polyradiculoneuropathy; Amyotrophic lateral sclerosis
• ISSN: 1568-9972; 1568-9972; 1873-0183
• DOI: 10.1016/j.autrev.2017.05.015

Abstract Autophagy is a metabolically-central process that is crucial in diverse areas of cell physiology. It ensures a fair balance between life and death molecular and cellular flows, and any disruption in this vital intracellular pathway can have consequences leading to major diseases such as cancer, metabolic and neurodegenerative disorders, and cardiovascular and pulmonary diseases. Recent pharmacological studies have shown evidence that small molecules and peptides able to activate or inhibit autophagy might be valuable therapeutic agents by down- or up-regulating excessive or defective autophagy, or to modulate normal autophagy to allow other drugs to repair some cell alteration or destroy some cell subsets (e.g. in the case of cancer concurrent treatments). Here, we provide an overview of neuronal autophagy and of its potential implication in some inflammatory diseases of central and peripheral nervous systems. Based on our own studies centred on a peptide called P140 that targets autophagy, we highlight the validity of autophagy processes, and in particular of chaperone-mediated autophagy, as a particularly pertinent pathway for developing novel selective therapeutic approaches for treating some neuronal diseases. Our findings with the P140 peptide support a direct cross-talk between autophagy and certain central and peripheral neuronal diseases. They also illustrate the fact that autophagy alterations are not evenly distributed across all organs and tissues of the same individual, and can evolve in different stages along the disease course.