Effects of LRSAM1 on TDP-43 in Patients With ALS скачать в хорошем качестве

Effects of LRSAM1 on TDP-43 in Patients With ALS

Takayuki Shirakawa, PhD, Research Scientist at Mitsubishi Tanabe Pharma, discusses the effects of LRSAM1 on TDP-43 in patients with amyotrophic lateral sclerosis (ALS). ALS, also referred to as "Lou Gehrig's disease," is a motor neuron disease that leads to muscle control and movement problems. There are various types of ALS that are distinguished by symptoms and, in some cases, genetic causes. Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or difficulty chewing or swallowing. As the disease progresses, people become weaker and are eventually wheelchair-dependent. Trans-activation response DNA-binding protein of 43 kDa (TDP-43) is a major component of ALS. The protein is responsible for mRNA and DNA binding, regulating mRNA splicing, stability, and translation, as well as gene transcription. As a possible driver of ALS pathophysiology, targeting this protein is thought to be a beneficial therapy pathway. The goal of the study was to evaluate the effects of LRSAM1 on TDP-43 pathophysiology and cytotoxicity in patients with ALS. LRSAM1 causes the degradation of cytoplasmic TDP-43, reducing neuronal toxicity. It was observed that LRSAM1 co-localizes with TDP-43 in neurons of postmortem human spinal cords. In patients with iPSC-derived neurons, LRSAM1 was able to improve TDP-43 pathophysiology, exert neuroprotective effects, and induce the degradation of cytotoxic C-terminal fragments of TDP-43.