ArticleNeurobiology of aging2013
Adenosine monophosphate-activated protein kinase overactivation leads to accumulation of α-synuclein oligomers and decrease of neurites.
Article in Neurobiology of aging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Metformin and Cognitive Performance in Patients With Type 2 Diabetes: An Umbrella Review.Neuropsychopharmacology reports · 2025Pooled it
- Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis.BMJ open diabetes research & care · 2020 · on this mapPooled it
- Inhibition of Abnormal Elevated α-Synuclein Ameliorates Dopaminergic Neuron Degeneration in Parkinson's Disease Mouse Model.Aging cell · 2026Article
- Roles of lactate and protein lactylation in neurogenesis and neurodegenerative disease.Journal of translational medicine · 2026Review
- Exploring the impacts of type 2 diabetes and metformin use on Parkinson's disease: Mendelian randomization analysis and a national cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Brain-muscle axis regulation of neuroinflammation and sarcopenia in Parkinson's disease: the bridging role of lactylation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Gastrodin inhibits hexokinase-2 mediated glycolysis to rescue rotenone-damaged PC12 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- CK and LRRK2 Involvement in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Metformin role in Parkinson's disease: a double-sword effect.Molecular and cellular biochemistry · 2024Review
- NADJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Inhibition of abnormal C/EBPβ/α-Syn signaling pathway through activation of Nrf2 ameliorates Parkinson's disease-like pathology.Aging cell · 2023Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- The Inhibition of Zinc Excitotoxicity and AMPK Phosphorylation by a Novel Zinc Chelator, 2G11, Ameliorates Neuronal Death Induced by Global Cerebral Ischemia.Antioxidants (Basel, Switzerland) · 2022Article
- Suppression of abnormal α-synuclein expression by activation of BDNF transcription ameliorates Parkinson's disease-like pathology.Molecular therapy. Nucleic acids · 2022Article
- Butyric Acid Precursor Tributyrin Modulates Hippocampal Synaptic Plasticity and Prevents Spatial Memory Deficits: Role of PPARγ and AMPK.The international journal of neuropsychopharmacology · 2022Article
- Dose-Response Association of Metformin with Parkinson's Disease Odds in Type 2 Diabetes Mellitus.Pharmaceutics · 2022Article
- Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases.Molecules (Basel, Switzerland) · 2022Review
- MPTP-induced mouse model of Parkinson's disease: A promising direction of therapeutic strategies.Bosnian journal of basic medical sciences · 2021Review
- Apoptotic Neuron-Derived Histone Amyloid Fibrils Induce α-Synuclein Aggregation.Molecular neurobiology · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
Neuronal inclusions of α-synuclein (α-syn), termed Lewy bodies, are a hallmark of Parkinson disease (PD). Increased α-syn levels can occur in brains of aging human and neurotoxin-treated mice. Because previous studies have shown increased brain lactate levels in aging brains, in PD affected subjects when compared with age-matched controls, and in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP), we tested the effects of lactate exposure on α-syn in a cell-based study. We demonstrated that (1) lactate treatment led to α-syn accumulation and oligomerization in a time- and concentration-dependent manner; (2) such alterations were mediated via adenosine monophosphate-activated protein kinase (AMPK) and associated with increasing cytoplasmic phosphorylated AMPK levels; (3) AMPK activation facilitated α-syn accumulation and phosphorylation; (4) lactate treatment or overexpression of the active form of AMPK decreased α-syn turnover and neurite outgrowth; and (5) Lewy body-bearing neurons displayed abnormal cytoplasmic distribution of phosphorylated AMPK, which normally is located in nuclei. Together, our results suggest that chronic neuronal accumulation of α-syn induced by lactate-triggered AMPK activation in aging brains might be a novel mechanism underlying α-synucleinopathies in PD and related disorders.
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