Publications by authors named "M Delenclos"
Investigating the Pathogenic Interplay of Alpha-Synuclein, Tau, and Amyloid Beta in Lewy Body Dementia: Insights from Viral-Mediated Overexpression in Transgenic Mouse Models.
Biomedicines
October 2023
Lewy body dementia (LBD) is an often misdiagnosed and mistreated neurodegenerative disorder clinically characterized by the emergence of neuropsychiatric symptoms followed by motor impairment. LBD falls within an undefined range between Alzheimer's disease (AD) and Parkinson's disease (PD) due to the potential pathogenic synergistic effects of tau, beta-amyloid (Aβ), and alpha-synuclein (αsyn). A lack of reliable and relevant animal models hinders the elucidation of the molecular characteristics and phenotypic consequences of these interactions.
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- - The study developed a novel toolkit using mutant methionyl-tRNA synthetase (MetRS) to isolate proteins secreted by mesenchymal stromal cells (MSCs) in mixed cultures, which is important for understanding tissue repair.
- - By integrating MetRS into various cell types and using click chemistry, researchers were able to successfully profile the secretome of MSCs, highlighting changes when co-cultured with different conditions, like lipopolysaccharide-treated cells.
- - This new methodology allows for enhanced investigation of MSC responses to diseases and could lead to revelations about tissue regeneration and repair mechanisms in a range of cell types derived from induced pluripotent stem cells (iPSCs).
Article Synopsis
- Intracytoplasmic inclusions of alpha-synuclein (αsyn) are key features in neurological disorders like Parkinson's disease, where reducing αsyn levels is an important goal for treatment.
- * Honokiol (HKL), a compound from magnolia bark with neuroprotective effects, was tested to see if it can lower αsyn levels in various experimental models, including human cells and mouse neurons.
- * The study found that HKL effectively reduces αsyn protein and gene expression through post-transcriptional mechanisms, suggesting it could be a valuable strategy to slow the progression of Parkinson's disease and related conditions.
Alpha-synuclein (αsyn) aggregates are pathological features of several neurodegenerative conditions including Parkinson disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA). Accumulating evidence suggests that mitochondrial dysfunction and impairments of the autophagic-lysosomal system can contribute to the deposition of αsyn, which in turn may interfere with health and function of these organelles in a potentially vicious cycle. Here we investigated a potential convergence of αsyn with the PINK1-PRKN-mediated mitochondrial autophagy pathway in cell models, αsyn transgenic mice, and human autopsy brain.
View Article and Find Full Text PDFMesenchymal stromal cells (MSCs) have a dynamic secretome that plays a critical role in tissue repair and regeneration. However, studying the MSC secretome in mixed-culture disease models remains challenging. This study aimed to develop a mutant methionyl-tRNA synthetase-based toolkit (MetRS ) to selectively profile secreted proteins from MSCs in mixed-culture systems and demonstrate its potential for investigating MSC responses to pathological stimulation.
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