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Control of Autophagy in Parkinson’s Disease

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Toxicity and Autophagy in Neurodegenerative Disorders

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 9))

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a dysregulation of cellular degradation system. An accumulation of misfolded proteins has been founded in the brains of parkinsonian patients, causing neuroinflammation and oxidative stress, and leading to a progressive neurodegeneration. Autophagy plays an important role in the progression of PD. In this chapter, we analyze the relationship of different types of autophagy (microautophagy, chaperone-mediated autophagy (CMA) and macroautophagy) with the oxidative stress and with several proteins involved in PD, showing deregulation of these degradative processes when these proteins are mutated. Also, we show a possible therapeutic alternative based on autophagy inducers that might be a potential drug for PD treatment.

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Abbreviations

ARE:

Antioxidant response element

Atgs:

Autophagy-related genes

AV:

Autophagic vacuole

CCCP:

Carbonyl cyanide m-chlorophenyl hydrazone

Δψm:

Mitochondrial membrane potential

ΔN-PINK1:

Cleaved PINK1

CMA:

Chaperone mediated autophagy

CNS:

Central nervous system

COR:

C-terminal of ROC

DA:

Dopamine

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulatde kinase

Fbxo7:

F-box protein 7

FCCP:

Carbonyl cyanide p-trifluoromethoxyphenylhydrazone

FL-PINK1:

Full-length PINK1; GSH, glutathione

Hsc70:

Heat-shock cognate 70

Hsp90:

Heat shock proteins 90

JDP2:

Jun dimerization protein 2

Keap1:

Kelch-like ECH-associated protein 1

L-DOPA:

L-3,4-dihydroxyphenylalanine

LAMP2A :

Lysosomal associated membrane protein-2A

LB:

Lewy body

LC3:

Microtubule-associated protein 1 light chain 3

LRR:

Leucine-rich repeat

LRRK2:

Leucine rich-repeat-kinase 2

MAO-B:

monoamine oxidase B

MAPK:

Mitogen-activated protein kinase

MafK:

v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog K

Mfn:

Mitofusin

MPP+ :

1-methyl-7-phenylpyridine

MPTP:

1-methyl–4-phenyl-1,2,3,6-tetrahidropyridine

mTOR:

Mammalian target of rapamycin

NK-B:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells

NRF-1:

Nuclear respiratory factor 1

Nrf2:

Nuclear factor (erythroid-derived)-like 2

6-OHDA:

6-hidroxydopamine

PARL:

Presenilin-associated rhomboid-like

PARIS:

Parkin interacting substrate

PARL:

Presenelin-associated rhomboid-like

PBR:

Ring-in-between-ring; PD, Parkinson’s disease

PGC-1α:

Peroxisome proliferator-activated receptor gamma

PI3K:

Phosphoinositide-3-kinase

PINK1:

Phosphatase and tensin homolog (PTEN)-induced kinase 1

PP2A:

Protein phosphatase type 2A

PQ:

Paraquat

RING:

Really interesting new gene domain

ROC:

Ras of complex proteins

ROS:

Reactive oxygen species

SMAF:

Small Maf proteins

SMERs:

Small molecule enhancers of rapamycin

α-syn:

α-synuclein

TFAM:

Mitochondrial transcription factor A

ULK1:

Unc-51-like kinase

UPS:

Ubiquitin proteasome system

UCH-L1:

Ubiquitin C-terminal hydrolase L1

VDAC:

Voltage-dependent anion channel

WT:

Wild type

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  1. Department of Biochemistry and Molecular Biologyand Genetics, Center for Biomedical Research Network Diseases Neurodegenerative (CIBERNED), University of Extremadura, Nursing and Occupational Therapy, Cáceres, Spain

    Rosa A. González-Polo, Rubén Gómez-Sánchez, Elisa Pizarro-Estrella, Sokhna M. S. Yakhine-Diop, Mario Rodríguez-Arribas & José M. Fuentes

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González-Polo, R., Gómez-Sánchez, R., Pizarro-Estrella, E., Yakhine-Diop, S., Rodríguez-Arribas, M., Fuentes, J. (2015). Control of Autophagy in Parkinson’s Disease. In: Fuentes, J. (eds) Toxicity and Autophagy in Neurodegenerative Disorders. Current Topics in Neurotoxicity, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-319-13939-5_6

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