Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease

Macroautophagy, an evolutionary conserved catabolic process in the eukaryotic cell, regulates cellular homeostasis and plays a decisive role in self-engulfing proteins, protein aggregates, dysfunctional or damaged organelles, and invading pathogens. Growing evidence from in vivo and in vitro models...

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Main Authors: Irene Sanchez-Mirasierra, Saurav Ghimire, Sergio Hernandez-Diaz, Sandra-Fausia Soukup
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.921314/full
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author Irene Sanchez-Mirasierra
Saurav Ghimire
Sergio Hernandez-Diaz
Sandra-Fausia Soukup
author_facet Irene Sanchez-Mirasierra
Saurav Ghimire
Sergio Hernandez-Diaz
Sandra-Fausia Soukup
author_sort Irene Sanchez-Mirasierra
collection DOAJ
description Macroautophagy, an evolutionary conserved catabolic process in the eukaryotic cell, regulates cellular homeostasis and plays a decisive role in self-engulfing proteins, protein aggregates, dysfunctional or damaged organelles, and invading pathogens. Growing evidence from in vivo and in vitro models shows that autophagy dysfunction plays decisive role in the pathogenesis of various neurodegenerative diseases, including Parkinson’s disease (PD). PD is an incurable and second most common neurodegenerative disease characterised by neurological and motor dysfunction accompanied of non-motor symptoms that can also reduce the life quality of patients. Despite the investment in research, the aetiology of the disease is still unknown and the therapies available are aimed mostly at ameliorating motor symptoms. Hence, therapeutics regulating the autophagy pathway might play an important role controlling the disease progression, reducing neuronal loss and even ameliorating non-motor symptoms. In this review, we highlight potential therapeutic opportunities involved in different targeting options like an initiation of autophagy, Leucine-rich repeat kinase 2 (LRRK2) inhibition, mitophagy, lysosomes, lipid metabolism, immune system, gene expression, biomarkers, and also non-pharmacological interventions. Thus, strategies to identify therapeutics targeting the pathways modulating autophagy might hold a future for therapy development against PD.
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spelling doaj.art-24bce31c99cd478e84d4526616e7e9272022-12-22T01:20:08ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-07-011010.3389/fcell.2022.921314921314Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s DiseaseIrene Sanchez-MirasierraSaurav GhimireSergio Hernandez-DiazSandra-Fausia SoukupMacroautophagy, an evolutionary conserved catabolic process in the eukaryotic cell, regulates cellular homeostasis and plays a decisive role in self-engulfing proteins, protein aggregates, dysfunctional or damaged organelles, and invading pathogens. Growing evidence from in vivo and in vitro models shows that autophagy dysfunction plays decisive role in the pathogenesis of various neurodegenerative diseases, including Parkinson’s disease (PD). PD is an incurable and second most common neurodegenerative disease characterised by neurological and motor dysfunction accompanied of non-motor symptoms that can also reduce the life quality of patients. Despite the investment in research, the aetiology of the disease is still unknown and the therapies available are aimed mostly at ameliorating motor symptoms. Hence, therapeutics regulating the autophagy pathway might play an important role controlling the disease progression, reducing neuronal loss and even ameliorating non-motor symptoms. In this review, we highlight potential therapeutic opportunities involved in different targeting options like an initiation of autophagy, Leucine-rich repeat kinase 2 (LRRK2) inhibition, mitophagy, lysosomes, lipid metabolism, immune system, gene expression, biomarkers, and also non-pharmacological interventions. Thus, strategies to identify therapeutics targeting the pathways modulating autophagy might hold a future for therapy development against PD.https://www.frontiersin.org/articles/10.3389/fcell.2022.921314/fullautophagyParkinson’s diseaseautophagy modulatorsPD causative proteinspotential therapeutic avenues
spellingShingle Irene Sanchez-Mirasierra
Saurav Ghimire
Sergio Hernandez-Diaz
Sandra-Fausia Soukup
Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
Frontiers in Cell and Developmental Biology
autophagy
Parkinson’s disease
autophagy modulators
PD causative proteins
potential therapeutic avenues
title Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
title_full Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
title_fullStr Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
title_full_unstemmed Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
title_short Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
title_sort targeting macroautophagy as a therapeutic opportunity to treat parkinson s disease
topic autophagy
Parkinson’s disease
autophagy modulators
PD causative proteins
potential therapeutic avenues
url https://www.frontiersin.org/articles/10.3389/fcell.2022.921314/full
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