BMB Reports 2017; 50(7): 345-354  https://doi.org/10.5483/BMBRep.2017.50.7.069
Therapeutic implication of autophagy in neurodegenerative diseases
Md. Ataur Rahman1 & Hyewhon Rhim1,2,*
1Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, 2Department of Neuroscience, Korea University of Science and Technology, Daejeon 34113, Korea
Correspondence to: Tel: +82-2-958-5923; Fax: +82-2-958-6937; E-mail: hrhim@kist.re.kr
Received: April 10, 2017; Published online: July 31, 2017.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
Autophagy, a catabolic process necessary for the maintenance of intracellular homeostasis, has recently been the focus of numerous human diseases and conditions, such as aging, cancer, development, immunity, longevity, and neurodegeneration. However, the continued presence of autophagy is essential for cell survival and dysfunctional autophagy is thought to speed up the progression of neurodegeneration. The actual molecular mechanism behind the progression of dysfunctional autophagy is not yet fully understood. Emerging evidence suggests that basal autophagy is necessary for the removal of misfolded, aggregated proteins and damaged cellular organelles through lysosomal mediated degradation. Physiologically, neurodegenerative disorders are related to the accumulation of amyloid β peptide and α-synuclein protein aggregation, as seen in patients with Alzheimer's disease and Parkinson's disease, respectively. Even though autophagy could impact several facets of human biology and disease, it generally functions as a clearance for toxic proteins in the brain, which contributes novel insight into the pathophysiological understanding of neurodegenerative disorders. In particular, several studies demonstrate that natural compounds or small molecule autophagy enhancer stimuli are essential in the clearance of amyloid β and α-synuclein deposits. Therefore, this review briefly deliberates on the recent implications of autophagy in neurodegenerative disorder control, and emphasizes the opportunities and potential therapeutic application of applied autophagy.
Keywords: Aggregate-prone proteins, Amyloid beta peptide, Autophagic flux, Clearance of toxic compounds, Neurodegenerative disorders
Figures
Fig. 1. Regulation of autophagy signaling pathway. Autophagy may initiate deprivation of nutrients or growth factors which activate AMPK and/or inhibition of mTORC1, leading to stimulation of ULK complex (FIP200 and ATG13). Beclin-1 become phosphorylated, leading to VPS34 activation and then initiation of phagophore formation. VPS34 complex function comprises a regulatory subunit like VPS15 (p150) and Beclin-1, their connection being with other regulatory factors e.g. AMBRA, ATG14, UVRAG, and BIF-1. Atg5–Atg12 conjugation involves Atg7 and Atg10 to form a complex, Atg12-atg5-Atg16 influences the formation of phagophores. Atg5 and Atg12 forms a complex with Atg16, which acts like an E3-function towards LC3-PE assembly (LC3-II). This has a role in the initiation of phagophore formation. LC3-II is a particular autophagy indicator marker which is eventually disrupted by autolysosomes. Autophagosome maturation also involves fusion with lysosomes which are mediated by Rab7, ESCRT and SNARE proteins, eventually leading to cargo degradation and recycling of nutrients and metabolites.


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