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In recent years, neurological and neurodegenerative disorders research has focused on altered molecular mechanisms in search of potential pharmacological targets, e.g., imbalances in mechanisms of response to oxidative stress, inflammation, apoptosis, autophagy, proliferation, differentiation, migration, and neuronal plasticity, which occur in less common neurological and neurodegenerative pathologies (Huntington disease, multiple sclerosis, fetal alcohol spectrum disorders, and Down syndrome). Here, we assess the effects of different catechins (particularly of epigalocatechin-3-gallate, EGCG) on these disorders, as well as their use in attenuating age-related cognitive decline in healthy individuals. Antioxidant and free radical scavenging properties of EGCG -due to their phenolic hydroxyl groups-, as well as its immunomodulatory, neuritogenic, and autophagic characteristics, makes this catechin a promising tool against neuroinflammation and microglia activation, common in these pathologies. Although EGCG promotes the inhibition of protein aggregation in experimental Huntington disease studies and improves the clinical severity in multiple sclerosis in animal models, its efficacy in humans remains controversial. EGCG may normalize DYRK1A (involved in neural plasticity) overproduction in Down syndrome, improving behavioral and neural phenotypes. In neurological pathologies caused by environmental agents, such as FASD, EGCG enhances antioxidant defense and regulates placental angiogenesis and neurodevelopmental processes. As demonstrated in animal models, catechins attenuate age-related cognitive decline, which results in improvements in long-term outcomes and working memory, reduction of hippocampal neuroinflammation, and enhancement of neuronal plasticity; however, further studies are needed. Catechins are valuable compounds for treating and preventing certain neurodegenerative and neurological diseases of genetic and environmental origin. However, the use of different doses of green tea extracts and EGCG makes it difficult to reach consistent conclusions for different populations.
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http://dx.doi.org/10.3390/nu13072232 | DOI Listing |
Cell Rep
September 2025
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address:
Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production.
View Article and Find Full Text PDFBehav Brain Res
September 2025
Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address:
Glutamate-mediated excitotoxicity represents a common pathomechanism in neurological disorders. As the predominant glutamate transporter in the central nervous system, glutamate transporter 1 (GLT-1, known as EAAT2 in humans) plays a crucial role in maintaining glutamate homeostasis and preventing excitotoxicity through its Na⁺-dependent transport mechanism. Key functions of GLT-1 include reducing extracellular glutamate concentration, regulating calcium homeostasis, suppressing oxidative stress, preserving mitochondrial integrity, and modulating neuroinflammatory processes by limiting microglial activation.
View Article and Find Full Text PDFBiomed Pharmacother
September 2025
Department and Graduate Institute of Pharmacology, College of Pharmacy, National Defense Medical University, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan; School of Pharmacy, College of Pharmacy, National Defense M
Parkinson's disease (PD) is characterized by chronic neuroinflammation and progressive dopaminergic neurodegeneration, driven primarily by the activation of microglia and associated apoptotic pathways. The intermediate-conductance calcium-activated potassium channel KCNN4 has recently emerged as a potential therapeutic target, yet its role in chronic neurodegenerative conditions remains underexplored. In this study, we investigated whether pharmacological inhibition of KCNN4 using TRAM-34 can modulate both inflammatory and apoptotic responses in an LPS-induced mouse model of PD.
View Article and Find Full Text PDFCell Mol Life Sci
September 2025
Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, Ürümqi, 830054, Xinjiang, China.
Microglial activation-induced neuroinflammation and impaired neuronal mitophagy are recognized as pivotal pathogeneses in Parkinson's disease (PD). However, the role of microglial mitophagy in microglial activation during PD development remains unclear, and therapeutic interventions targeting this interaction are lacking. Rhapontigenin (Rhap), a stilbenoid enriched in Vitis vinifera, exhibits dual anti-neuroinflammatory and mitophagy-enhancing properties, but its therapeutic potential and mechanisms in PD are unexplored.
View Article and Find Full Text PDFCerebellum
September 2025
Department of Neurology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Multiple system atrophy (MSA) is a progressive, adult-onset neurodegenerative disorder involving autonomic failure, cerebellar ataxia, and parkinsonism. Patients often require invasive interventions, such as gastrostomy or tracheostomy, and sudden death is common. This study aimed to elucidate patterns of invasive treatment and identify risk factors for tracheostomy or sudden death within 5 years of onset.
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