Endovascular Stem Cell Therapy Post Stroke Rescues Neurons from Endoplasmic Reticulum Stress-Induced Apoptosis by Modulating Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B Signaling.

Ischemic stroke is devastating, with serious long-term disabilities affecting millions of people worldwide. Growing evidence has shown that mesenchymal stem cells (MSCs) administration after stroke provides neuroprotection and enhances the quality of life in stroke patients. Previous studies from our lab have shown that 1 × 10 MSCs administered intra-arterially (IA) at 6 h post stroke provide neuroprotection through the modulation of inflammasome and calcineurin signaling.

Cell Death Pathways in Ischemic Stroke and Targeted Pharmacotherapy.

Ischemic stroke is one of the significant causes of morbidity and mortality, affecting millions of people across the globe. Cell injury in the infarct region is an inevitable consequence of focal cerebral ischemia. Subsequent reperfusion exacerbates the harmful effect and increases the infarct volume.

Endoplasmic reticulum-mitochondria crosstalk: from junction to function across neurological disorders.

The endoplasmic reticulum (ER) and mitochondria are fundamental organelles highly interconnected with a specialized set of proteins in cells. ER-mitochondrial interconnections form specific microdomains, called mitochondria-associated ER membranes, that have been found to play important roles in calcium signaling and lipid homeostasis, and more recently in mitochondrial dynamics, inflammation, and autophagy. It is not surprising that perturbations in ER-mitochondria connections can result in the progression of disease, especially neurological disorders; hence, their architecture and regulation are crucial in determining the fate of cells and disease.

Evolving Evidence of Calreticulin as a Pharmacological Target in Neurological Disorders.

Calreticulin (CALR), a lectin-like ER chaperone, was initially known only for its housekeeping function, but today it is recognized for many versatile roles in different compartments of a cell. Apart from canonical roles in protein folding and calcium homeostasis, it performs a variety of noncanonical roles, mostly in CNS development. In the past, studies have linked Calreticulin with various other biological components which are detrimental in deciding the fate of neurons.

Interplay between Mitophagy and Inflammasomes in Neurological Disorders.

Mitophagy and inflammasomes have a pivotal role in the development of neuropathology. Molecular mechanisms behind mitophagy and inflammasomes are well-understood, but lacunae prevail in understanding the crosstalk between them in various neurological disorders. As mitochondrial dysfunction is the prime event in neurodegeneration, the clearance of impaired mitochondria is one of the main tasks for maintaining cell integrity in the majority of neuropathologies.