Drug Development.

Background: TAR-DNA-binding protein 43 (TDP43), is a pathologic marker in neurodegenerative diseases including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The aggregation of TDP-43, a crucial RNA-binding protein, is a consequence of post-translational modifications (PTMs) that disrupt its normal function. PTMs such as phosphorylation and ubiquitination contribute to the aberrant accumulation of TDP-43 aggregates, leading to neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

Drug Development.

Background: The increased incidence of Alzheimer's disease (AD) rate represent an unmet medical need and thus critical for the development of novel molecular therapeutics. Recent work focusing on patients with apoE4 alleles has highlighted the association of brain cholesterol dysregulation with elevated pathological burden and neurodegeneration. These studies have highlighted the importance of the nuclear receptor Liver X receptor (LXR) for developing AD therapies.

Drug Development.

Background: Neurological disorders are at epidemic levels in the world today. Various proteins are being targeted for the development of novel molecular therapeutics; however, no small-molecule inhibitors have been discovered. Recent studies suggest that there are few molecules in clinical trials for various secretase (α, β, and γ), caspase, and calpain inhibitors.

Drug Development.

Background: Alzheimer's disease (AD) is characterized by hallmark amyloid plaques and neurofibrillary tangles as well as by a significant loss of myelin in the cerebral cortex and other brain regions, which contributes to neurodegeneration and cognitive decline. Remyelination, of the myelin sheath by oligodendrocytes, is a process that may be impaired in neurodegenerative diseases. Depending on the severity of the disease, there occurs loss or partial damage of the myelin sheath surrounding the neuron leading to memory deficits.

Factors associated with lower forced vital capacity in children and adults with Duchenne muscular dystrophy using non-invasive ventilation: a multicenter analysis.

Background: Reduced forced vital capacity (FVC) is associated with morbidity and mortality in individuals with Duchenne muscular dystrophy (DMD). Non-invasive ventilation (NIV) is often prescribed for the treatment of sleep-disordered breathing (SDB), and chronic respiratory insufficiency. Despite the common practice of initiating NIV later in the progression of DMD, the factors influencing FVC subsequent to the commencement of NIV remain unclear.