Subtle genomic DNA damage induces intraneuronal production of amyloid-β (1-42) by increasing β-secretase activity.

Aberrant accumulation of amyloid-β (Aβ) in brain is the major trigger for pathogenesis in Alzheimer's disease (AD). It is imperative to understand how Aβ attains such toxic levels in the brain parenchyma. We detected that a subtle and tolerable amount of DNA damage, related to aging, increased intraneuronal Aβ production both in cultured neuron and in cortex of rodent brain.

Smokeless tobacco induces toxicity and apoptosis in neuronal cells: a mechanistic evaluation.

Smokeless tobacco (SLT) or chewing tobacco has been a highly addictive practice in India across ages, posing major threat to the systemic health and possibly neurodegeneration. Earlier studies showed components of SLT could be harmful to neuronal health. However, mechanism of SLT in neurodegeneration remained unexplored.

Destabilization of β-amyloid aggregates by thrombin derived peptide: plausible role of thrombin in neuroprotection.

β-amyloid (Aβ) aggregates involved in Alzheimer's disease (AD) are resistant to proteases but could be destabilized by small peptides designed to target specific hydrophobic regions of Aβ that take part in aggregate assembly. Since thrombin and AD are intricately connected, and elastase modulates thrombin activity, elastase-digested thrombin peptides were verified for intervention in the Aβ-aggregation pathway. Intact or elastase-digested thrombin destabilized Aβ fibril, as demonstrated by thioflavin T assay.

The regulation of p53 up-regulated modulator of apoptosis by JNK/c-Jun pathway in β-amyloid-induced neuron death.

Neuronal loss in selective areas of brain underlies the pathology of Alzheimer's disease (AD). Recent evidences place oligomeric β-amyloid (Aβ) central to the disease. However, mechanism of neuron death in response to Aβ remains elusive.