Healthy Plasma Exosomes Exert Potential Neuroprotective Effects against Methylmalonic Acid-Induced Hippocampal Neuron Injury.
ACS Chem Neurosci
; 15(16): 3022-3033, 2024 Aug 21.
Article
em En
| MEDLINE
| ID: mdl-39026168
ABSTRACT
Exosomes have shown good potential for alleviating neurological deficits and delaying memory deterioration, but the neuroprotective effects of exosomes remain unknown. Methylmalonic acidemia is a metabolic disorder characterized by the accumulation of methylmalonic acid (MMA) in various tissues that inhibits neuronal survival and function, leading to accelerated neurological deterioration. Effective therapies to mitigate these symptoms are lacking. The purpose of this study was to explore the neuroprotective effects of plasma exosomes on cells and a mouse model of MMA-induced injury. We evaluated the ability of plasma exosomes to reduce the neuronal apoptosis, cross the blood-brain barrier, and affect various parameters related to neuronal function. MMA promoted cell apoptosis, disrupted the metabolic balance, and altered the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), and synaptophysin-1 (Syp-1), and these changes may be involved in MMA-induced neuronal apoptosis. Additionally, plasma exosomes normalized learning and memory and protected against MMA-induced neuronal apoptosis. Our findings indicate that neurological deficits are linked to the pathogenesis of methylmalonic acidemia, and healthy plasma exosomes may exert neuroprotective and therapeutic effects by altering the expression of exosomal microRNAs, facilitating neuronal functional recovery in the context of this inherited metabolic disease. Intravenous plasma-derived exosome treatment may be a novel clinical therapeutic strategy for methylmalonic acidemia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Fármacos Neuroprotetores
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Exossomos
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Hipocampo
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Ácido Metilmalônico
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
ACS Chem Neurosci
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA