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Cell Death Mechanisms of Neurodegeneration

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Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 15))

Abstract

There are common mechanisms shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation. This indicates that although the original cause may differ in individual diseases or even subtypes of certain disorders, these disrupted common cell functions and signaling, together with aging, may lead to final execution of cell death through similar pathways. The variable neurodegenerative disease symptoms are probably caused by the type, location, and connection of the cell populations that suffer from dysfunction and loss. Besides apoptosis, necroptosis, and autophagy, an important form of death termed parthanatos plays a prominent role in stroke and several neurodegenerative diseases, which is due to PARP-1 overactivation, PAR accumulation, nuclear translocation of the mitochondria protein AIF, and large-scale DNA cleavage. Understanding the mechanisms and interactions of cell death signaling will not only help to develop neuroprotective strategies to halt neurodegeneration, but also provide biomarkers for monitoring disease progression and recovery.

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Abbreviations

3-MA:

3-Methyladenine

6-OHDA:

6-Hydroxydopamine

Aβ:

β-Amyloid peptide

AD:

Alzheimer’s disease

AIF:

Apoptosis-inducing factor

AIMP2:

Aminoacyl-tRNA synthetase complex interacting multifunctional protein-2

ALS:

Amyotrophic lateral sclerosis

AMPK:

AMP-activated protein kinase

APP:

Amyloid precursor protein

ARH3:

ADP-ribosylhydrolase 3

BRCT:

BRCA1 C-terminal

CNS:

Central nervous system

DPQ:

3,4-Dihydro-5-(4-(1-piperidinyl)butoxyl)-1(2H)-isoquinolinone

HD:

Huntington’s disease

IFNγ:

Interferon gamma

KO:

Knock out

LPS:

Lipopolysaccharide

MCAO:

Middle cerebral artery occlusion

MNNG:

N-Methyl-N′-nitro-N-nitrosoguanidine

MPP+:

1-Methyl-4-phenylpyridinium

MPT:

Mitochondrial permeability transition

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MS:

Multiple sclerosis

mTOR:

Mechanistic target of rapamycin

NAD+:

Oxidized nicotinamide adenine dinucleotide

Nec-1:

Necrostatin-1

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NLS:

Nuclear localization sequence

NMDA:

N-Methyl-d-aspartate

nNOS:

Neuronal nitric oxide synthase

NO:

Nitric oxide

OGD:

Oxygen glucose deprivation

P53:

Tumor protein 53

PAAN:

Parthanatos-dependent AIF-associated nuclease

PAR:

Poly(ADP-ribose)

PARP1:

Poly(ADP-ribose) polymerase 1

PARG:

Poly(ADP-ribose) glycohydrolase

PBM:

PAR-binding motif

PBZF:

PAR-binding zinc finger

PD:

Parkinson’s disease

PI3K:

Phosphoinositide3-kinase

PSM:

PARP signature motif

ROS:

Reactive oxygen species

siRNA:

Small interfering RNA

SOD1:

Superoxide dismutase 1

TH:

Tyrosine-hydroxylase

TNF:

Tumor necrosis factor

TNFR1:

TNFα receptor 1

RIPK1:

Receptor-interacting protein kinase 1

RIPK3:

Receptor-interacting protein kinase 3

Z-VAD-fmk:

N-Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone

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Acknowledgments

This work was supported by grants from MSCRFII-0429 and MSCRFII-0125 to V.L.D. 2013-MSCRF-0028 to J.F. and NIH/NINDS NS67525 to T.M.D. and V.L.D. T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases. We thank I-Hsun Wu for drawing the figures.

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Authors and Affiliations

  1. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Jing Fan Ph.D, Ted M. Dawson M.D., Ph.D. & Valina L. Dawson Ph.D.

  2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Jing Fan Ph.D, Ted M. Dawson M.D., Ph.D. & Valina L. Dawson Ph.D.

  3. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Ted M. Dawson M.D., Ph.D. & Valina L. Dawson Ph.D.

  4. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Ted M. Dawson M.D., Ph.D.

  5. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Valina L. Dawson Ph.D.

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  1. Jing Fan Ph.D
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  2. Ted M. Dawson M.D., Ph.D.
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  3. Valina L. Dawson Ph.D.
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Correspondence to Valina L. Dawson Ph.D. .

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Editors and Affiliations

  1. University of Melbourne Florey Institute of Neuroscience and Mental Health, Parkville, Australia

    Philip Beart

  2. Pediatrics and Pharmacology Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Michael Robinson

  3. School of Life Sciences Bradford School of Pharmacy, University of Bradford, Bradford, United Kingdom

    Marcus Rattray

  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Nicholas J. Maragakis

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Fan, J., Dawson, T.M., Dawson, V.L. (2017). Cell Death Mechanisms of Neurodegeneration. In: Beart, P., Robinson, M., Rattray, M., Maragakis, N. (eds) Neurodegenerative Diseases. Advances in Neurobiology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-57193-5_16

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