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Updated: Jun 20, 2025
Enrichment of Astrocyte-Derived Extracellular Vesicles from Human Plasma
Published on: August 3, 2022
Healthy Plasma Exosomes Exert Potential Neuroprotective Effects against Methylmalonic Acid-Induced Hippocampal Neuron
Wei Zhou1,2, Huizhong Li2, Jinxiu Song3
1Research Center for Biochemistry and Molecular Biology and Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou 221004, P.R China.
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.
Insights
Plasma exosomes show promise in protecting brain cells and improving memory in methylmalonic acidemia (MMA). This inherited metabolic disorder causes neurological damage, but exosome therapy may offer a novel treatment strategy.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Cell Biology
Background:
- Methylmalonic acidemia (MMA) is a metabolic disorder causing neurotoxicity due to methylmalonic acid accumulation.
- Neurological deficits and memory deterioration are key features of MMA, with limited therapeutic options.
- Exosomes, small vesicles involved in intercellular communication, have potential neuroprotective roles.
Purpose of the Study:
- To investigate the neuroprotective effects of plasma exosomes in a mouse model of MMA-induced neurological injury.
- To evaluate the capacity of plasma exosomes to mitigate neuronal apoptosis and improve neuronal function in MMA.
- To explore the therapeutic potential of plasma exosomes for methylmalonic acidemia.
Main Methods:
- Utilized cell and mouse models of methylmalonic acidemia (MMA).
- Administered plasma exosomes and assessed their ability to cross the blood-brain barrier.
- Evaluated exosome effects on neuronal apoptosis, learning, memory, and expression of key proteins (Bcl-2, Bax, Syp-1).
Main Results:
- MMA induced neuronal apoptosis, disrupted metabolic balance, and altered expression of apoptosis-related proteins and synaptophysin-1.
- Plasma exosomes effectively reduced neuronal apoptosis and normalized learning and memory deficits in MMA mice.
- Exosomes demonstrated the ability to cross the blood-brain barrier and exert neuroprotective effects.
Conclusions:
- Neurological deficits in methylmalonic acidemia are linked to disease pathogenesis.
- Plasma exosomes exhibit significant neuroprotective and therapeutic potential for MMA.
- Intravenous exosome therapy represents a promising novel clinical strategy for methylmalonic acidemia.
