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Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia

Schizophrenia (SZ) is a deleterious brain disorder affecting cognition, emotion and reality perception. The most widely accepted neurochemical-hypothesis is the imbalance of neurotransmitter-systems. Depleted GABAergic-inhibitory function might produce a regionally-located dopaminergic and glutamate...

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Autores principales: Morén, Constanza, Treder, Nina, Martínez-Pinteño, Albert, Rodríguez, Natàlia, Arbelo, Néstor, Madero, Santiago, Gómez, Marta, Mas, Sergi, Gassó, Patricia, Parellada, Eduard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686909/
https://www.ncbi.nlm.nih.gov/pubmed/36421461
http://dx.doi.org/10.3390/antiox11112275
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author Morén, Constanza
Treder, Nina
Martínez-Pinteño, Albert
Rodríguez, Natàlia
Arbelo, Néstor
Madero, Santiago
Gómez, Marta
Mas, Sergi
Gassó, Patricia
Parellada, Eduard
author_facet Morén, Constanza
Treder, Nina
Martínez-Pinteño, Albert
Rodríguez, Natàlia
Arbelo, Néstor
Madero, Santiago
Gómez, Marta
Mas, Sergi
Gassó, Patricia
Parellada, Eduard
author_sort Morén, Constanza
collection PubMed
description Schizophrenia (SZ) is a deleterious brain disorder affecting cognition, emotion and reality perception. The most widely accepted neurochemical-hypothesis is the imbalance of neurotransmitter-systems. Depleted GABAergic-inhibitory function might produce a regionally-located dopaminergic and glutamatergic-storm in the brain. The dopaminergic-release may underlie the positive psychotic-symptoms while the glutamatergic-release could prompt the primary negative symptoms/cognitive deficits. This may occur due to excessive synaptic-pruning during the neurodevelopmental stages of adolescence/early adulthood. Thus, although SZ is not a neurodegenerative disease, it has been suggested that exaggerated dendritic-apoptosis could explain the limited neuroprogression around its onset. This apoptotic nature of SZ highlights the potential therapeutic action of anti-apoptotic drugs, especially at prodromal stages. If dysregulation of apoptotic mechanisms underlies the molecular basis of SZ, then anti-apoptotic molecules could be a prodromal therapeutic option to halt or prevent SZ. In fact, risk alleles related in apoptotic genes have been recently associated to SZ and shared molecular apoptotic changes are common in the main neurodegenerative disorders and SZ. PRISMA-guidelines were considered. Anti-apoptotic drugs are commonly applied in classic neurodegenerative disorders with promising results. Despite both the apoptotic-hallmarks of SZ and the widespread use of anti-apoptotic targets in neurodegeneration, there is a strikingly scarce number of studies investigating anti-apoptotic approaches in SZ. We analyzed the anti-apoptotic approaches conducted in neurodegeneration and the potential applications of such anti-apoptotic therapies as a promising novel therapeutic strategy, especially during early stages.
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spelling pubmed-96869092022-11-25 Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia Morén, Constanza Treder, Nina Martínez-Pinteño, Albert Rodríguez, Natàlia Arbelo, Néstor Madero, Santiago Gómez, Marta Mas, Sergi Gassó, Patricia Parellada, Eduard Antioxidants (Basel) Review Schizophrenia (SZ) is a deleterious brain disorder affecting cognition, emotion and reality perception. The most widely accepted neurochemical-hypothesis is the imbalance of neurotransmitter-systems. Depleted GABAergic-inhibitory function might produce a regionally-located dopaminergic and glutamatergic-storm in the brain. The dopaminergic-release may underlie the positive psychotic-symptoms while the glutamatergic-release could prompt the primary negative symptoms/cognitive deficits. This may occur due to excessive synaptic-pruning during the neurodevelopmental stages of adolescence/early adulthood. Thus, although SZ is not a neurodegenerative disease, it has been suggested that exaggerated dendritic-apoptosis could explain the limited neuroprogression around its onset. This apoptotic nature of SZ highlights the potential therapeutic action of anti-apoptotic drugs, especially at prodromal stages. If dysregulation of apoptotic mechanisms underlies the molecular basis of SZ, then anti-apoptotic molecules could be a prodromal therapeutic option to halt or prevent SZ. In fact, risk alleles related in apoptotic genes have been recently associated to SZ and shared molecular apoptotic changes are common in the main neurodegenerative disorders and SZ. PRISMA-guidelines were considered. Anti-apoptotic drugs are commonly applied in classic neurodegenerative disorders with promising results. Despite both the apoptotic-hallmarks of SZ and the widespread use of anti-apoptotic targets in neurodegeneration, there is a strikingly scarce number of studies investigating anti-apoptotic approaches in SZ. We analyzed the anti-apoptotic approaches conducted in neurodegeneration and the potential applications of such anti-apoptotic therapies as a promising novel therapeutic strategy, especially during early stages. MDPI 2022-11-17 /pmc/articles/PMC9686909/ /pubmed/36421461 http://dx.doi.org/10.3390/antiox11112275 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Morén, Constanza
Treder, Nina
Martínez-Pinteño, Albert
Rodríguez, Natàlia
Arbelo, Néstor
Madero, Santiago
Gómez, Marta
Mas, Sergi
Gassó, Patricia
Parellada, Eduard
Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia
title Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia
title_full Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia
title_fullStr Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia
title_full_unstemmed Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia
title_short Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia
title_sort systematic review of the therapeutic role of apoptotic inhibitors in neurodegeneration and their potential use in schizophrenia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686909/
https://www.ncbi.nlm.nih.gov/pubmed/36421461
http://dx.doi.org/10.3390/antiox11112275
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