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The Molecular Mechanisms Between Autophagy and Apoptosis: Potential Role in Central Nervous System Disorders

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Abstract

Autophagy involves degradation of dysfunctional cellular components through the actions of lysosomes. Apoptosis is the process of programmed cell death involving a series of characteristic cell changes. Autophagy and apoptosis, as self-destructive processes, play an important role in the pathogenesis of neurological diseases; and a crosstalk between “self-eating” (autophagy) and “self-killing” (apoptosis) plays an important role in pathological cellular adaptation. Expert knowledge of autophagy and apoptosis has increased in recent years, particularly in regards to cellular and molecular mechanisms. The crosstalk between autophagy and apoptosis was partially uncovered and several key molecules, including Bcl-2 family members, Beclin 1, and p53 were identified. However, the precise mechanisms of such a crosstalk remain to be elucidated. This current review article aims to summarize key mediators of the autophagy-apoptosis crosstalk in pathological conditions, and to highlight recent advances in the field, as well as to discuss further investigations and therapeutic potentials of manipulating those mechanisms in central nervous system diseases.

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Abbreviations

Ambra1:

Activating molecule in Beclin 1-regulated autophagy

Atg:

Autophagy-related

CNS:

Central nervous system

Cyt c:

Cytochrome c

DRAM:

Damage-regulated autophagy modulator

MOMP:

Mitochondrial outer membrane permeabilization

mTOR:

Mammalian target of rapamycin

PB1:

Phox and Bem1p

PI3K:

Phosphatidylinositol 3-kinase

PUMA:

p53-upregulated modulator of apoptosis

TSC:

Tuberous sclerosis

ULK1:

Unc-51-like kinase 1

UVRAG:

UV irradiation resistance-associated tumor suppressor gene

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Acknowledgments

This study was supported by National Natural Science Foundation of China (No. 81171096 and No. 81371433) to Jian-Min Zhang.

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Authors and Affiliations

  1. Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China

    Hai-Jian Wu, Jian-Min Zhang & Sheng Chen

  2. Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Jia-Li Pu

  3. Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA

    Paul. R. Krafft

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  1. Hai-Jian Wu
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Correspondence to Sheng Chen.

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Hai-Jian Wu and Jia-Li Pu contributed equally to the work.

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Wu, HJ., Pu, JL., Krafft, P.R. et al. The Molecular Mechanisms Between Autophagy and Apoptosis: Potential Role in Central Nervous System Disorders. Cell Mol Neurobiol 35, 85–99 (2015). https://doi.org/10.1007/s10571-014-0116-z

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