withaferin-a and Frontotemporal-Lobar-Degeneration

Withaferin-A, an active withanolide derived from the medicinal herbal plant Withania somnifera induces autophagy, reduces TDP-43 proteinopathy, and improves cognitive function in transgenic mice expressing mutant TDP-43 modelling FTLD. TDP-43 is a nuclear DNA/RNA-binding protein with cellular functions in RNA transcription and splicing. Abnormal cytoplasmic aggregates of TDP-43 occur in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). To date, no effective treatment is available for TDP-43 proteinopathies. Here, we tested the effects of withaferin-A (WFA), an active withanolide extracted from the medicinal herbal plant Withania somnifera, in a transgenic mouse model of FTLD expressing a genomic fragment encoding mutant TDP-43

Topics: Animals; Avoidance Learning; Blotting, Western; Brain; Cells, Cultured; Cognition; Disease Models, Animal; DNA-Binding Proteins; Female; Fluorescent Antibody Technique; Frontotemporal Lobar Degeneration; Male; Mice; Mice, Transgenic; NF-kappa B; Signal Transduction; Withanolides

Abnormal cytoplasmic mislocalization of transactive response DNA binding protein 43 (TARDBP or TDP-43) in degenerating neurons is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous work suggested that nuclear factor kappa B (NF-κB) may constitute a therapeutic target for TDP-43-mediated disease. Here, we investigated the effects of root extract of Withania somnifera (Ashwagandha), an herbal medicine with anti-inflammatory properties, in transgenic mice expressing a genomic fragment encoding human TDP-43

Topics: Amyotrophic Lateral Sclerosis; Animals; Avoidance Learning; Cells, Cultured; Cytokines; Disease Models, Animal; DNA-Binding Proteins; Encephalitis; Female; Frontotemporal Lobar Degeneration; Male; Mice; Mice, Transgenic; Microglia; Motor Activity; Neuromuscular Junction; Neurons; NF-kappa B; Plant Extracts; Rotarod Performance Test; Spinal Cord; TDP-43 Proteinopathies; Withania