Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Oct. 6, 2020

Gangliosides are glycosphingolipids highly abundant in the nervous system, and carry most of sialic acid residues brain. enriched cell membrane microdomains (“lipid rafts”) play important roles modulation proteins ion channels, signaling communication among cells. The importance gangliosides brain is highlighted by fact that loss function mutations ganglioside biosynthetic enzymes result severe neurodegenerative disorders, often characterized very early or childhood onset. In addition, changes profile (i.e. relative abundance specific gangliosides) were reported healthy ageing common neurological conditions, including Huntington’s disease (HD), Alzheimer’s (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS), stroke, multiple epilepsy. At least HD, PD some forms epilepsy, experimental evidence strongly suggests a potential role pathogenesis treatment. this review, we will summarize functions crucial to maintain health, review levels occur major conditions discuss their contribution cellular dysfunctions pathogenesis. Finally, beneficial exerted gangliosides, GM1 particular, models clinical trials.

Language: Английский

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The cellular and molecular basis of major depressive disorder: towards a unified model for understanding clinical depression

Molecular Biology Reports, Journal Year: 2019, Volume and Issue: 47(1), P. 753 - 770

Published: Oct. 14, 2019

Language: Английский

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New Avenues for the Treatment of Huntington’s Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8363 - 8363

Published: Aug. 4, 2021

Huntington’s disease (HD) is a neurodegenerative disorder caused by CAG expansion in the HD gene. The characterized neurodegeneration, particularly striatum and cortex. first symptoms usually appear mid-life include cognitive deficits motor disturbances that progress over time. Despite being genetic with known cause, several mechanisms are thought to contribute neurodegeneration HD, numerous pre-clinical clinical studies have been conducted currently underway test efficacy of therapeutic approaches targeting some these varying degrees success. Although current trials may lead identification or refinement treatments likely improve quality life those living major efforts continue be invested at level, testing novel show promise as disease-modifying strategies. This review offers detailed overview approved treatment options for this concludes discussing potential shown studies, including increasing neurotropic support, modulating autophagy, epigenetic manipulations, use nanocarriers stem cells.

Language: Английский

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Prevalence and clinical aspects of depression in Parkinson’s disease: A systematic review and meta‑analysis of 129 studies

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 141, P. 104749 - 104749

Published: June 21, 2022

Depression is one of the most important non-motor symptoms in Parkinson's disease (PD), but its prevalence and related clinical characteristics are unclear. To this end, we performed a systematic review meta-analysis based on 129 studies, including 38304 participants from 28 countries. Overall, depression PD was 38 %. When compared with patients without depression, those had younger age onset, lower education level, longer duration, higher UPDRS-III, H&Y staging scale, MMSE, SE-ADL scores. We observed that associated female patients, carrying GBA1 mutation, freezing gait (FOG), apathy, anxiety fatigue. Our results suggest an independent, frequent symptom PD, appearing early stage persisting throughout duration. In addition, several motor appeared to be negatively impacted quality life.

Language: Английский

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Characterizing Heterogeneity in Neuroimaging, Cognition, Clinical Symptoms, and Genetics Among Patients With Late-Life Depression

JAMA Psychiatry, Journal Year: 2022, Volume and Issue: 79(5), P. 464 - 464

Published: March 9, 2022

Importance

Late-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such might aid elucidating etiological mechanisms and support precision individualized medicine.

Objective

To cross-sectionally longitudinally delineate disease-related LLD associated with neuroanatomy, cognitive functioning, symptoms, genetic profiles.

Design, Setting, Participants

The Imaging-Based Coordinate System for Aging Neurodegenerative Diseases (iSTAGING) study an international multicenter consortium investigating brain aging pooled harmonized data from 13 studies more than 35 000 participants, including a subset of individuals major depressive disorder. Multimodal sample (N = 996), neuroimaging, neurocognitive assessments, genetics, were analyzed this study. A semisupervised clustering method (heterogeneity through discriminative analysis) was applied to regional gray matter (GM) volumes derive dimensional representations. Data collected July 2017 2020 December 2021.

Main Outcomes Measures

Two dimensions identified LLD-associated voxelwise GM maps, white (WM) fractional anisotropy, phenotype, genetics.

Results

total 501 participants (mean [SD] age, 67.39 [5.56] years; 332 women) 495 healthy control 66.53 [5.16] 333 included. Patients dimension 1 demonstrated relatively preserved anatomy without WM disruptions relative individuals. In contrast, patients 2 showed widespread atrophy integrity disruptions, along impairment higher severity. Moreover, de novo independent variant (rs13120336; chromosome: 4, 186387714; minor allele, G) significantly (odds ratio, 2.35; SE, 0.15;P 3.14 ×10⁸) but not 2. significant single-nucleotide variant–based heritability 18% 27% within the general population 12 518 UK Biobank). having longitudinal measurements, those experienced rapid change age (Cohenf² 0.03;P .02) likely progress Alzheimer disease .03) compared 1431 7224 scans Alzheimer's Disease Neuroimaging Initiative [ADNI], Baltimore Longitudinal Study [BLSA], Biomarkers Older Controls at Risk Dementia [BIOCARD] sets).

Conclusions Relevance

This into distinct neuroanatomical, cognitive, clinical, approach provides potential mechanism relevance latent possible mechanisms, outcomes, responses interventions.

Language: Английский

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Global, regional, and national burden of neurological disorders in 204 countries and territories worldwide

Journal of Global Health, Journal Year: 2023, Volume and Issue: 13

Published: Nov. 29, 2023

We aimed to determine the incidence and disability-adjusted life-years (DALYs) of neurological disorders worldwide from 1990 2019.We obtained age-standardised DALY rates in 204 countries territories 2019 Global Burden Disease (GBD) database. determined trends stratified by age, sex, region, country, Social Development Index (SDI) risk factors contributing DALYs associated with these disorders.The largest increases 1990-2019 occurred four regions (East Asia: estimated annual percentage change (EAPC) = 0.19, tropical Latin America: EAPC 0.07, Southern 0.03, Western Europe: 0.03) three (China: 0.20, Ecuador: 0.13, Italy: 0.13). observed for Parkinson disease, idiopathic epilepsy, bipolar disorder, Alzheimer disease other dementias. High-SDI showed highest depression, motor neuron disorders.There is a need control increase East Asia, America, Europe, particularly China, Ecuador, Italy.

Language: Английский

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Neurobiology of depression in Parkinson’s disease: Insights into epidemiology, molecular mechanisms and treatment strategies

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 85, P. 101840 - 101840

Published: Jan. 2, 2023

Language: Английский

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Antioxidant and Anti-Inflammatory Effects of Carotenoids in Mood Disorders: An Overview

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 676 - 676

Published: March 9, 2023

Depression has a multifactorial etiology comprising family history and unemployment. This review aims to summarize the evidence available for antioxidant anti-inflammatory effects of carotenoids in mood disorders. article’s methodologies were based on search PubMed database all linked published papers. Epidemiological studies indicate that diet rich vegetables, fruits, nuts, fish, olive oil may prevent development depression. Antioxidant supplementation been found combat various stress-induced psychiatric disorders, including depression anxiety. A growing body indicates have both anti-inflammatory. Studies also suggest poor dietary intake, particularly low intakes fruit vegetables high fast food other convenience foods, increase risk developing Thus, interventions potential help mitigate mental health decline general population those with Considering effects, it is expected they might exert promising antidepressant effect. Nevertheless, further (including interventional mechanistic studies) assessing effect preventing alleviating symptoms are needed.

Language: Английский

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Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 574 - 574

Published: March 5, 2024

Neurodegeneration poses a significant challenge for the fields of neuroscience and medicine, as it is underlying cause development advancement numerous neurodegenerative psychiatric disorders [...]

Language: Английский

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The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Huntington's disease (HD) is a currently incurable neurogenerative disorder and typically characterized by progressive movement (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which depression), peripheral symptoms gastrointestinal dysfunction). There are no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some hold promising potential. HD subjects often burdened chronic diarrhea, constipation, esophageal gastric inflammation, susceptibility to diabetes. Our understanding the microbiota–gut–brain axis its infancy growing evidence from preclinical clinical studies suggests role gut microbial population imbalance (gut dysbiosis) pathophysiology. The brain can communicate through enteric nervous system, immune vagus nerve, microbiota‐derived‐metabolites including short‐chain fatty acids, bile branched‐chain amino acids. This review summarizes supporting demonstrating alterations bacterial fungal composition that may be associated HD. We focus on mechanisms dysbiosis compromise health, thus triggering neuroinflammatory responses, further highlight outcomes attempts modulate microbiota as therapeutic strategies Ultimately, we discuss dearth data need more longitudinal translational this nascent field. suggest future directions improve our association between microbes pathogenesis other ‘brain body disorders’.

Language: Английский

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