دورية أكاديمية
Neurodegenerative Etiology of Aromatic L-Amino Acid Decarboxylase Deficiency: a Novel Concept for Expanding Treatment Strategies.
العنوان: | Neurodegenerative Etiology of Aromatic L-Amino Acid Decarboxylase Deficiency: a Novel Concept for Expanding Treatment Strategies. |
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المؤلفون: | Sternberg Z; Jacobs School of Medicine and Biomedical Sciences, Buffalo Medical Center, Buffalo, NY, 14203, USA. zs2@buffalo.edu. |
المصدر: | Molecular neurobiology [Mol Neurobiol] 2024 May; Vol. 61 (5), pp. 2996-3018. Date of Electronic Publication: 2023 Nov 13. |
نوع المنشور: | Journal Article; Review |
اللغة: | English |
بيانات الدورية: | Publisher: Humana Press Country of Publication: United States NLM ID: 8900963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1182 (Electronic) Linking ISSN: 08937648 NLM ISO Abbreviation: Mol Neurobiol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Clifton, NJ : Humana Press, c1987- |
مواضيع طبية MeSH: | Aromatic-L-Amino-Acid Decarboxylases*/*deficiency, Aromatic-L-Amino-Acid Decarboxylases*/metabolism , Aromatic-L-Amino-Acid Decarboxylases*/genetics , Amino Acid Metabolism, Inborn Errors*/therapy , Amino Acid Metabolism, Inborn Errors*/genetics , Neurodegenerative Diseases*/therapy, Humans ; Animals |
مستخلص: | Aromatic l-amino acid decarboxylase deficiency (AADC-DY) is caused by one or more mutations in the DDC gene, resulting in the deficit in catecholamines and serotonin neurotransmitters. The disease has limited therapeutic options with relatively poor clinical outcomes. Accumulated evidence suggests the involvement of neurodegenerative mechanisms in the etiology of AADC-DY. In the absence of neurotransmitters' neuroprotective effects, the accumulation and the chronic presence of several neurotoxic metabolites including 4-dihydroxy-L-phenylalanine, 3-methyldopa, and homocysteine, in the brain of subjects with AADC-DY, promote oxidative stress and reduce the cellular antioxidant and methylation capacities, leading to glial activation and mitochondrial dysfunction, culminating to neuronal injury and death. These pathophysiological processes have the potential to hinder the clinical efficacy of treatments aimed at increasing neurotransmitters' synthesis and or function. This review describes in detail the mechanisms involved in AADC-DY neurodegenerative etiology, highlighting the close similarities with those involved in other neurodegenerative diseases. We then offer novel strategies for the treatment of the disease with the objective to either reduce the level of the metabolites or counteract their prooxidant and neurotoxic effects. These treatment modalities used singly or in combination, early in the course of the disease, will minimize neuronal injury, preserving the functional integrity of neurons, hence improving the clinical outcomes of both conventional and unconventional interventions in AADC-DY. These modalities may not be limited to AADC-DY but also to other metabolic disorders where a specific mutation leads to the accumulation of prooxidant and neurotoxic metabolites. (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
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فهرسة مساهمة: | Keywords: Antioxidants; Inborn error of metabolism; Methylation status; Neuroinflammation; Parkinson’s disease; Rare genetic disease; Sulfur-containing compounds |
المشرفين على المادة: | EC 4.1.1.28 (Aromatic-L-Amino-Acid Decarboxylases) |
SCR Disease Name: | Aromatic amino acid decarboxylase deficiency |
تواريخ الأحداث: | Date Created: 20231112 Date Completed: 20240424 Latest Revision: 20240625 |
رمز التحديث: | 20240625 |
DOI: | 10.1007/s12035-023-03684-2 |
PMID: | 37953352 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1559-1182 |
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DOI: | 10.1007/s12035-023-03684-2 |