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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. The molecular identity of the specialized proteins regulating ER–mitochondrial crosstalk remains unclear. Our discussion here describes the physical and functional crosstalk between these two dynamic organelles and emphasizes the outcome of altered ER–mitochondrial interconnections in neurological disorders.

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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 5 MSCs administered intra-arterially (IA) at 6 h post stroke provide neuroprotection through the modulation of inflammasome and calcineurin signaling. Ischemic stroke induces endoplasmic reticulum (ER) stress, which exacerbates the pathology. The current study intends to understand the involvement of brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling in preventing apoptosis induced by ER stress post stroke following IA MSCs administration. Ischemic stroke was induced in ovariectomized female Sprague Dawley rats. The MSCs were administered IA, and animals were sacrificed at 24 h post stroke. Infarct area, neurological deficit score, motor coordination, and biochemical parameters were evaluated. The expression of various genes and proteins was assessed. An inhibition study was also carried out to confirm the involvement of BDNF/TrkB signaling in ER stress-induced apoptosis. IA-administered MSCs improved functional outcomes, reduced infarct area, increased neuronal survival, and normalized biochemical parameters. mRNA and protein expression of ER stress markers were reduced, while those of BDNF and TrkB were increased. Reduction in ER stress-mediated apoptosis was also observed. The present study shows that IA MSCs administration post stroke provides neuroprotection and can modulate ER stressmediated apoptosis via the BDNF/TrkB signaling pathway.

Stroke is a debilitating condition which is also the second leading cause of death and disability worldwide. Despite the benefits and promises shown by numerous neuroprotective agents in animal stroke models, their clinical translation has not been a complete success. Hence, search for treatment options have directed researchers towards utilising stem cells. Mitochondria has a major involvement in the pathophysiology of stroke and a number of other conditions. Stem cells have shown the ability to transfer mitochondria to the damaged cells and to help revive cell energetics in the recipient cell. The present review discusses how stem cells could be employed to protect neurons and mitochondria in stroke and also the various mechanisms involved in neuroprotection.

Myeloperoxidase (MPO) is a protein present in azurophilic granules, macrophages, and neutrophils that are released into extracellular fluid (ECF) during inflammation. MPO releases hypochlorous acid (HOCl) and other chlorinated species. It is derived from hydrogen peroxide (HO) showing response during inflammatory conditions and plays a role in the immune defense against pathogens. MPO may show unwanted effects by indirectly increasing the formation of reactive nitrogen species (RNS), reactive oxygen species (ROS), and tumor necrosis factor alpha (TNF-α) leading to inflammation and oxidative stress. As neuroinflammation is one of the inevitable biological components among most of neurological disorders, MPO and its receptor may be explored as candidates for future clinical interventions. The purpose of this review is to provide an overview of the pathophysiological characteristics of MPO and further explore the possibilities to target it for clinical use. Targeting MPO is promising and may open an avenue to act as a biomarker for diagnosis with defined risk stratification in patients with various neurological disorders.