Role of Autophagy in Alzheimer's disease

Jaekwang Kim, Hyejin Yoon, Jungsu Kim

Research output: Contribution to journalArticle

Abstract

Autophagy is a tightly regulated lysosomal degradation/recycling pathway, critical for cellular homeostasis, such as neuronal survival and death. Impaired autophagic function has been reported in several neurodegenerative diseases, such as Parkinson's, Huntington's and Alzheimer's disease (AD). AD is the most common cause of dementia in the elderly and it is characterized by progressive memory loss and cognitive decline along with synaptic dysfunction. Accumulations of amyloid β (Aβ) and tau proteins are two major neuropathological hallmarks of AD. In addition, accumulation of autophagic vacuoles and other autophagic pathology are evident in dystrophic neurites of AD brains. A series of studies has suggested that autophagy is involved in metabolism of Aβ and tau. Moreover, presenilin (PS), a core subunit of γ-secretase complex, has been demonstrated to play an important role in autophagy at the level of lysosomal proteolysis. In spite of several therapeutic approaches through modulation of autophagic pathway, inconsistent results among studies have made it difficult to determine whether autophagy induction will be beneficial or detrimental for AD pathogenesis. Therefore, roles of autophagy in AD need to be further investigated to develop therapeutic strategies in the future.

Original languageEnglish (US)
Pages (from-to)55-66
Number of pages12
JournalCurrent Enzyme Inhibition
Volume9
Issue number1
DOIs
StatePublished - May 14 2013
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Autophagy
  • Beclin
  • Rapamycin
  • mTOR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Drug Discovery

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