title: Autophagy and apoptosis dysfunction in neurodegenerative disorders.
abstract: Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. Autophagy encompasses pathways that target long-lived cytosolic proteins and damaged organelles. It involves a sequential set of events including double membrane formation, elongation, vesicle maturation and finally delivery of the targeted materials to the lysosome. Apoptotic cell death is best described through its morphology. It is characterized by cell rounding, membrane blebbing, cytoskeletal collapse, cytoplasmic condensation, and fragmentation, nuclear pyknosis, chromatin condensation/fragmentation, and formation of membrane-enveloped apoptotic bodies, that are rapidly phagocytosed by macrophages or neighboring cells. Neurodegenerative disorders are becoming increasingly prevalent, especially in the Western societies, with larger percentage of members living to an older age. They have to be seen not only as a health problem, but since they are care-intensive, they also carry a significant economic burden. Deregulation of autophagy plays a pivotal role in the etiology and/or progress of many of these diseases. Herein, we briefly review the latest findings that indicate the involvement of autophagy in neurodegenerative diseases. We provide a brief introduction to autophagy and apoptosis pathways focusing on the role of mitochondria and lysosomes. We then briefly highlight pathophysiology of common neurodegenerative disorders like Alzheimer's diseases, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Then, we describe functions of autophagy and apoptosis in brain homeostasis, especially in the context of the aforementioned disorders. Finally, we discuss different ways that autophagy and apoptosis modulation may be employed for therapeutic intervention during the maintenance of neurodegenerative disorders.
authors.affiliation: Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada; Manitoba Institute of Child Health, Department of Physiology, University of Manitoba, Winnipeg, Canada; St. Boniface Research Centre, University of Manitoba, Winnipeg, Canada.
authors.forename: Saeid
authors.initials: S
authors.lastname: Ghavami
authors.affiliation: Department of Biochemistry, Recombinant Protein Laboratory, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Shahla
authors.initials: S
authors.lastname: Shojaei
authors.affiliation: Manitoba Institute of Child Health, Department of Physiology, University of Manitoba, Winnipeg, Canada; Hospital for Sick Children Research Institute, Department of Physiology and Experimental Medicine, University of Toronto, Canada.
authors.forename: Behzad
authors.initials: B
authors.lastname: Yeganeh
authors.affiliation: Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Sudharsana R
authors.initials: SR
authors.lastname: Ande
authors.affiliation: Department of Clinical and Experimental Medicine (IKE), Integrative Regenerative Medicine Center (IGEN), Division of Cell Biology, Linkoping University, Linkoping, Sweden.
authors.forename: Jaganmohan R
authors.initials: JR
authors.lastname: Jangamreddy
authors.affiliation: INSERM U845, Research Center "Growth & Signaling" Paris Descartes University Medical School, France.
authors.forename: Maryam
authors.initials: M
authors.lastname: Mehrpour
authors.affiliation: Department of Clinical and Experimental Medicine (IKE), Integrative Regenerative Medicine Center (IGEN), Division of Cell Biology, Linkoping University, Linkoping, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Christoffersson
authors.affiliation: Department of Clinical and Experimental Medicine (IKE), Integrative Regenerative Medicine Center (IGEN), Division of Cell Biology, Linkoping University, Linkoping, Sweden; Department of Biology, Faculty of Sciences, Tunis University, Tunis, Tunisia.
authors.forename: Wiem
authors.initials: W
authors.lastname: Chaabane
authors.affiliation: Young Researchers Club, Ardabil Branch, Islamic Azad University, Ardabil, Iran.
authors.forename: Adel Rezaei
authors.initials: AR
authors.lastname: Moghadam
authors.affiliation: Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada; Manitoba Institute of Child Health, Department of Physiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Hessam H
authors.initials: HH
authors.lastname: Kashani
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; Cellular and Molecular Biology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: Department of Biochemistry, Recombinant Protein Laboratory, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: aaowji@yahoo.com.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Owji
authors.affiliation: Department of Clinical and Experimental Medicine (IKE), Integrative Regenerative Medicine Center (IGEN), Division of Cell Biology, Linkoping University, Linkoping, Sweden. Electronic address: mjelos@gmail.com.
authors.forename: Marek J
authors.initials: MJ
authors.lastname: Łos
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D001927:Brain Diseases / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000503:physiopathology*
keywords: AD; AIF; ALS; AMBRA; AMP-activated protein kinase; AMPA; AMPK; APP; ATG; Alzheimer's diseases; Apo-E; Aβ; BDNF; CMA; ER; ESCRT; HD; HEK293; HIP-1; Htt; Huntingtin interacting protein; Huntingtin protein; Huntington's disease; InsP(6)Ks; LAMP; LC3; LRPPRC; MAP15; Mitochondria dysfunction; N-methyl-d-aspartate; NCCD; NMDA; PCD; PD; PINK-1; PON 1–3; PTEN-induced putative kinase 1; Parkinson's disease; Porteopathies; RCAN-1; RSVA314; RSVA405; RUBICON; RUN domain and cysteine rich domain containing; Resveratrol; TAR DNA-binding protein 43kDa; TDP-43-kDa; Trehalose; UPS; UVRAG; VCP; X-box binding protein-1; XBP-1; activating molecule in Beclin-1-regulated autophagy; alpha-synuclein; amyloid beta precursor protein; amyloid-beta; amyotrophic lateral sclerosis; apolipo-protein E; apoptosis-inducing factor; autophagosome-associated light chain 3; autphagy related genes; brain-derived neurotrophic factor; chaperon-mediated autophagy; endoplasmic reticulum; endosomal sorting complexes required for transport; human embryonic kidney 293 cells; inositol hexakisphosphate kinases; lysosomal associated membrane proteins; mHtt; mPTP; mTOR; mammalian target of rapamycin; microtubule-associated protein 15; mitochondrial permeability transition pore; mitochondrion-associated leucine-rich PPR-motif containing protein; mutant Huntingtin protein; nomenclature committee on cell death; p53; pQ; paraxonase enzymes; poly-glutamine; programmed cell death; regulator of calcineurin-1; tumor protein 53; ubiquitin-proteasome system; ultra-violet radiation resistance-associated gene; valosin-containing protein; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; α-syn