• Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

    • Md. Sahab Uddin
      Department of Pharmacy, Southeast University, Bangladesh
    • Anna Stachowiak
      Department of Experimental Embryology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences
    • Abdullah Al Mamun
      Department of Pharmacy, Southeast University, Bangladesh
    • Nikolay T. Tzvetkov
      Institute of Molecular Biology “Roumen Tsanev”, Department of Molecular Biology and Biochemical Pharmacology, Bulgarian Academy of Sciences
    • Shinya Takeda
      Department of Clinical Psychology, Tottori University Graduate School of Medical Sciences
    • Atanas G. Atanasov
      Department of Pharmacognosy, Faculty of Life Sciences, University of Vienna
    • Leandro B. Bergantin
      Department of Pharmacology, Federal University of São Paulo
    • Mohamed M. Abdel-Daim
      Department of Pharmacology, Suez Canal University
    • Adrian M. Stankiewicz
      Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences
  • Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.

  • PDF

  • http://phaidra.univie.ac.at/o:1032912

  • Article

  • Published Version

  • 2018

  • 10

  • Frontiers Media SA

  • English

  • Open access

  • CC BY Attribution 4.0 International
    © 2018 Uddin, Stachowiak, Mamun, Tzvetkov, Takeda, Atanasov, Bergantin, Abdel-Daim and Stankiewicz

  • 1663-4365

  • autophagy; Alzheimer’s disease; amyloid beta; tau