Fundamental changes in the composition and distribution of lipids within the brain are believed to contribute to the cognitive decline associated with Alzheimer's disease (AD). The mechanisms by which these changes in lipid composition affect cellular function and ultimately cognition are not well understood. Although "candidate gene" approaches can provide insight into the effects of dysregulated lipid metabolism they require a preexisting understanding of the molecular targets of individual lipid species. In this report we combine unbiased gene expression profiling with a genome-wide chemogenomic screen to identify the mitochondria as an important downstream target of PC(O-16:0/2:0), a neurotoxic lipid species elevated in AD. Further examination revealed that PC(O-16:0/2:0) similarly promotes a global increase in ceramide accumulation in human neurons which was associated with mitochondrial-derived reactive oxygen species (ROS) and toxicity. These findings suggest that PC(O-16:0/2:0)-dependent mitochondrial dysfunction may be an underlying contributing factor to the ROS production associated with AD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725818 | PMC |
| http://dx.doi.org/10.1038/srep19332 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Topical review: Ocular surface abnormalities in neurodegenerative disorders.
Optom Vis Sci
January 2025
School of Optometry and Vision Science, UNSW Sydney, Sydney, New South Wales, Australia.
Significance: In an aging population, the number of people living with neurodegenerative disease is projected to increase. It is vital to develop reliable, noninvasive biomarkers to detect disease onset and monitor progression, and there is a growing body of research into the ocular surface as a potential source of such biomarkers.
Background: This article reviews the potential of in vivo corneal confocal microscopy and tear fluid analysis as tools for biomarker development.
Calcium Signalling in Neurological Disorders, with Insights from Miniature Fluorescence Microscopy.
Cells
December 2024
Neural Dynamics Laboratory, Department of Medicine, The University of Melbourne, Melbourne, VIC 3052, Australia.
Neurological disorders (NDs), such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and schizophrenia, represent a complex and multifaceted health challenge that affects millions of people around the world. Growing evidence suggests that disrupted neuronal calcium signalling contributes to the pathophysiology of NDs. Additionally, calcium functions as a ubiquitous second messenger involved in diverse cellular processes, from synaptic activity to intercellular communication, making it a potential therapeutic target.
View Article and Find Full Text PDFNeuropsychological test performance in mild cognitive impairment with Lewy bodies: A systematic review and meta-analysis.
Alzheimers Dement
January 2025
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Background: We sought to characterize the cognitive profile among individuals with mild cognitive impairment with Lewy bodies (MCI-LB) to help guide future clinical criteria.
Methods: Systematic review and meta-analysis included MCI-LB studies with cognitive data from PubMed, Embase, Web of Science, and PsycINFO (January 1990 to March 2023). MCI-LB scores were compared to controls, MCI due to Alzheimer's disease (MCI-AD), and dementia with Lewy bodies (DLB) groups with random-effects models.
Bibliometric Study of Periodontitis and Alzheimer's Disease: Trends, Collaboration, and Emerging Patterns.
J Contemp Dent Pract
September 2024
Bibliometrics, Evidence Evaluation and Systematic Reviews (BEERS) Group, Human Medicine Career, Universidad Científica del Sur, Lima, Peru, Phone: +5113171023, e-mail:
Aim: To perform a bibliometric study of periodontal disease and Alzheimer's disease (AD) focusing on trends, collaborative efforts, and emerging patterns.
Materials And Methods: From January 2018 to May 2024, an observational study was carried out utilizing metadata extracted from the Scopus database. A search methodology, specifically designed for this database, was developed using MeSH terms combined with Boolean operators such as "AND" and "OR".
Associations between lifelong cognitive reserve, Alzheimer's disease-related plasma biomarkers, and cognitive function in dementia-free older adults: A population-based study.
J Alzheimers Dis
January 2025
Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.
Background: Cognitive reserve (CR), typically measured through socio-behavioral proxies, can partially explain better cognitive performance despite underlying brain aging or neuropathology.
Objective: To examine the associations of CR with mild cognitive impairment (MCI) and cognitive function while considering Alzheimer's disease (AD)-related plasma biomarkers.
Methods: This population-based cross-sectional study included 4706 dementia-free individuals from MIND-China.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!