Compensatory lymphangiogenesis is required for edema resolution in zebrafish.

Edema, characterized by the accumulation of interstitial fluid, poses significant challenges in various pathological conditions. Lymphangiogenesis is critical in edema clearance, and delayed or inadequate lymphatic responses significantly hinder healing processes. However, real-time observation of dynamic changes in lymphangiogenesis during tissue repair in animal models has been challenging, leaving the mechanisms behind compensatory lymphatic activation for edema clearance largely unexplored.

Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson's disease.

Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson's disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous evaluations included whole-genome/exome sequencing, RNA sequencing, and in vivo studies, including a 39-week Good Laboratory Practice-compliant mouse safety study.

Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the loss of both upper and lower motor neurons, leading to progressive paralysis. Both genetic alterations and epigenetic modifications contribute to neuronal dysfunction in the pathogenesis of ALS. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear.

Loss of function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.

Genetic changes and epigenetic modifications are associated with neuronal dysfunction in the pathogenesis of neurodegenerative disorders. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear. Here, we identified an ALS-associated SNP located in the intronic region of (rs304152), residing in a putative enhancer element, using convolutional neural network.

Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis.

Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclerosis (fALS) forms 10% of the cases.

How Microglia Manages Non-cell Autonomous Vicious Cycling of Aβ Toxicity in the Pathogenesis of AD.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and a common form of dementia that affects cognition and memory mostly in aged people. AD pathology is characterized by the accumulation of β-amyloid (Aβ) senile plaques and the neurofibrillary tangles of phosphorylated tau, resulting in cell damage and neurodegeneration. The extracellular deposition of Aβ is regarded as an important pathological marker and a principal-agent of neurodegeneration.