Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies.

Ex vivo cellular system that accurately replicates sickle cell disease and β-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and β-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells.

Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach.

Accumulation of Aβ peptides forming plaque in various regions of the brain is a hallmark of Alzheimer's disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of Aβ-induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications.

Regional heterogeneity in mitochondrial function underlies region specific vulnerability in human brain ageing: Implications for neurodegeneration.

Selective neuronal vulnerability (SNV) of specific neuroanatomical regions such as frontal cortex (FC) and hippocampus (HC) is characteristic of age-associated neurodegenerative diseases (NDDs), although its pathogenetic basis remains unresolved. We hypothesized that physiological differences in mitochondrial function in neuroanatomical regions could contribute to SNV. To investigate this, we evaluated mitochondrial function in human brains (age range:1-90 y) in FC, striatum (ST), HC, cerebellum (CB) and medulla oblongata (MD), using enzyme assays and quantitative proteomics.

Aβ42 Expressing Model for Alzheimer's Disease: Quantitative Proteomics Identifies Altered Protein Dynamics of Relevance to Neurodegeneration.

Production and deposition of β-amyloid peptides (Aβ) are among the major hallmarks of the pathogenesis of Alzheimer's disease (AD). Mapping the altered protein dynamics associated with Aβ accumulation and neuronal damage may open up new avenues to innovation for drug target discovery in AD. Using quantitative proteomics, we report new findings from the amyloid beta-peptide with 42 amino acids (Aβ42) expressing model for AD compared to that of the wild-type flies.

Mapping Post-Translational Modifications in Brain Regions in Alzheimer's Disease Using Proteomics Data Mining.

Alzheimer's disease (AD) is a leading cause of dementia and a neurodegenerative disease. Proteomics and post-translational modification (PTM) analyses offer new opportunities for a comprehensive understanding of pathophysiology of brain in AD. We report here multiple PTMs in patients with AD, harnessing publicly available proteomics data from nine brain regions and at three different Braak stages of disease progression.

Molecular Targets from Traditional Medicines for Neuroprotection in Human Neurodegenerative Diseases.

Neurodegeneration is one of the greatest threats to global public health. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are among the major causes of chronic neurological conditions in the elderly populations. Hence, neuroprotection is at the epicenter of the current 21st-century research agenda in biomedicine.

Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells.

Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form.

Dissecting Alzheimer's Disease Molecular Substrates by Proteomics and Discovery of Novel Post-translational Modifications.

Alzheimer's disease (AD) is a common complex disease and a major public health burden in both developed and developing countries. Postgenomic technologies such as proteomics and intelligent mining of multi-omics Big Data offer new prospects for diagnostics and therapeutics innovation for AD. In this context, it is noteworthy that mass spectrometry (MS) data are often searched against proteomics databases to unravel the identity of protein biomarkers.

A network map of netrin receptor UNC5B-mediated signaling.

UNC-5 Homolog B (UNC5B) is a member of the dependence receptor family. This family of receptors can induce two opposite intracellular signaling cascades depending on the presence or absence of the ligand and is thus capable of driving two opposing processes. UNC5B signaling has been implicated in several cancers, where it induces cell death in the absence of its ligand Netrin-1 and promotes cell survival in its presence.