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Background: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Background: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.
View Article and Find Full Text PDFBackground: The hyperphosphorylation, mislocalization, and aggregation of the microtubule associated protein Tau (MAPT) is a driving force in tauopathies, a group of progressive, neurodegenerative disorders. These pathogenic intracellular aggregates, known as neurofibrillary tangles (NFTs), are a hallmark in several diseases such as frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's Disease. While anti-Tau immunotherapies emphasize the clearance of extracellular Tau aggregates, they do not address the intracellular accumulation of NFTs.
View Article and Find Full Text PDFBackground: Progranulin (GRN) plays a critical role in familial frontotemporal dementia (fFTD), where GRN haploinsufficiency leads to reduction in PGRN levels in the brain, resulting in degeneration of neurons in the frontal lobe of brain responsible for personality, language, and behavior. FTD is the most common dementia in people under 60. Sortilin (Sort1), expressed by neurons, endocytoses, and delivers PGRN rapidly to lysosomes for degradation.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The TREAT-AD centers aim to improve Alzheimer's Disease (AD) research by offering free, high-quality tools and technologies. Lyn is a tyrosine kinase that belongs to the Src family kinases. The expression of Lyn and its activity have been implicated in AD.
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