Positive allosteric modulators (PAMs) of the muscarinic acetylcholine M4 receptor show potential against schizophrenia because they can enhance endogenous acetylcholine signaling, which in turn may mitigate psychotic symptoms as well as improve attention and working memory in individuals with the disorder. However, the efficacy of a promising PAM, CVL-231, has been disappointing in clinical trials.
AC Immune SA has synthesized thiazolo[5,4-c]pyridine-4(5H)-one derivatives acting as TAR DNA-binding protein 43 (TARDBP; TDP-43) aggregation ligands reported to be useful for the diagnosis of amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, limbic-predominant age-related TDP-43 encephalopathy and traumatic encephalopathy.
Researchers at University of South China and collaborators have generated numerous carbamate-based N-benzoyl tryptamine derivatives for Alzheimer’s disease.
H. Lundbeck A/S and Contera Pharma A/S have entered into a strategic research collaboration designed to accelerate the discovery and development of innovative oligonucleotide-based medicines for serious neurological conditions with unmet needs.
Restrictive element-1 silencing transcription factor (REST) has key roles in neuronal differentiation, structural remodeling and plasticity, contributing to neuronal homeostasis in postnatal neurons. It acts as a suppressor of neuronal gene expression in stem and progenitor cells, and abnormal accumulation of it has been linked to several neurological disorders, like Huntington’s disease, epilepsy and stroke.
Do men’s and women’s brains age equally? Women are more often diagnosed with Alzheimer’s disease (AD) than men. Age is the primary known risk factor for AD prevalence, and both aging and AD are associated with brain atrophy, but it is still not clear whether men and women differ regarding brain decline in aging. There is mixed evidence regarding this topic, since most of the larger studies have shown an abrupt decay of total gray matter and hippocampal volume in men, but other studies have found steeper total gray matter decline in women.
Inhibiting human monoamine oxidase (MAO)-B to increase the availability of monoamine neurotransmitters is a clinically approved strategy for treating Parkinson’s disease, yet available inhibitors lack efficacy or increase risk of adverse events. Researchers at Hefei University of Technology and collaborators started from the clinically improved MAO-B inhibitor safinamide and generated various derivatives, among which [I] and [II] emerged as the most promising.
Researchers at Indian Institute of Technology (BHU) Varanasi and collaborators have designed inhibitors of cholinesterase based on benzothiazole-phenylpiperizine as a potential treatment for Alzheimer’s disease.
Researchers at Shanghai Jingxin Biopharmaceutical Co. Ltd. and Zhejiang Jingxin Pharmaceutical Co. Ltd. have divulged compounds acting as leucine-rich repeat kinase 2 (LRRK2; dardarin) inhibitors reported to be useful for the treatment of Parkinson’s disease.
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