Asset Details
Do you wish to reserve the book?
Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics
Do you wish to request the book?
Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Metabolic toxicity and neurological dysfunction in methylmalonic acidemia: from mechanisms to therapeutics
2025
Overview
Methylmalonic acidemia (MMAemia) is an inborn error of organic acid metabolism characterized by the accumulation of toxic metabolites—including methylmalonic acid (MMA), 2-methylcitric acid (2-MCA), propionic acid (PA), homocysteine (Hcy), ammonia, and lactate—due to defects in methylmalonyl-CoA mutase or impaired cobalamin metabolism. These metabolites exert profound effects on the central nervous system, contributing to neurological injury through tightly interconnected mechanisms, including mitochondrial dysfunction, neuroinflammation, and excitotoxicity. This review synthesizes current evidence on how these metabolites trigger neurological dysfunction, integrating findings from clinical studies, animal models, and cellular systems. We also highlight the increasingly recognized role of aberrant post-translational modifications (e.g., methylmalonylation, propionylation, lactylation) in disrupting metabolic network architecture and reprogramming cellular metabolism. Despite advances in supportive therapies, intracerebral metabolite accumulation remains a therapeutic challenge. We discuss emerging strategies targeting mitochondrial protection, redox homeostasis, and inflammation—including enzyme replacement, gene therapy, antioxidant regimens, and exosome-based delivery. A deeper mechanistic understanding of metabolite-driven neurotoxicity is critical to the development of targeted interventions that can improve neurological outcomes in MMAemia.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
Amino Acid Metabolism, Inborn Errors - complications
/ Amino Acid Metabolism, Inborn Errors - metabolism
/ Amino Acid Metabolism, Inborn Errors - therapy
/ Ammonia
/ Animals
/ Biomedical and Life Sciences
/ Enzymes
/ Humans
/ Methylmalonic Acid - metabolism
/ Nervous System Diseases - etiology
/ Nervous System Diseases - metabolism
/ Nervous System Diseases - therapy
/ Post-translational modification
/ Review
