Lysosomal membrane permeabilization (LMP) is observed under many pathological conditions, leading to cellular dysfunction and death. However, the mechanisms by which lysosomal membranes become leak...

Introduction: Mitophagy, the selective degradation of damaged mitochondria, is essential for maintaining cellular health and function, particularly in high-energy demanding post-mitotic cells like neurons and in microglial cells. Aging results in impaired mitophagy, leading to mitochondrial dysfunction, oxidative stress, the release of damage-associated proteins (DAMPs), and neuroinflammation, which contribute to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Mitochondrial dysfunction also contributes to the pathophysiology of depression by affecting synaptic plasticity, increasing neuroinflammation, and heightening oxidative stress. Aim: In this review, we summarize the recent developments on mechanisms of mitophagy, its therapeutic role in neuroprotection, and its implications in aging and neuroinflammation, complemented by future research requirements and implications. Result/Discussion: Therapeutic strategies that promote mitochondrial health, including enhancing mitophagy and mitochondrial biogenesis, show promise in treating neurodegenerative diseases and depression. Recent findings have emphasized therapeutic strategies to modulate mitophagy, such as pharmacological agents like urolithin A and rapamycin, genetic interventions such as PINK1/Parkin gene therapy, mitochondrial transplantation, and lifestyle and dietary interventions such as caloric restriction, exercise, and dietary supplements such as resveratrol and CoQ10. Key regulators of mitophagy, including the PINK1/Parkin pathway and various proteins like BNIP3, NIX, and FUNDC1, which facilitate the removal of damaged mitochondria, play a crucial role. Conclusions: These results highlight the importance of understanding the interplay between mitophagy and neuroinflammation and show that modulation of mitophagy can reduce oxidative stress and improve neuroinflammatory outcomes and depression in age-related neurodegenerative diseases. However, despite significant progress, challenges remain in understanding the underlying molecular mechanisms of mitophagy and its therapeutic regulation in aging disorders.

Controlling the proinflammatory response of microglia by targeting chemokines (C-C motif) receptor 2 (CCR2) could be an important therapeutic approach for Japanese encephalitis virus (JEV) infection. Here, through JEV infection to BV2 microglia and young BALB/c mice, we investigated that CCR2 is highly upregulated after JEV infection and plays a key role in determining microglia activation phenotype and associated with neurotoxic proinflammatory mediators of TNF-α and IFNγ. In addition, we found JEV infection to BV2 microglia causes an increase in microglial proliferation and cell body area at day 1 and day 3. Using the agonist molecule of CCR2 inhibition; RS102895, significantly reduces microglia reactive phenotype and nitric oxide production. Further, to define the role of CCR2 in functional responses of microglia and their activation phenotype, we performed in vitro cell scratch functional assay and ImageJ analysis. When compared with control, microglia cells showed a significant increase in elongated or rod-like activated phenotype in JEV-infected cells at 24 h post-infection and CCR2 inhibition significantly reduced the elongated activation phenotype induced by JEV infection, suggesting that CCR2 acts as a critical regulator for microglia activation phenotype after JEV infection. We found that JEV-infected mice treated with RS102895 had less microglia activation and reduced mRNA expression of CCR2 and proinflammatory mediators such as IFN-γ in cortical tissue. Collectively, our data indicate that CCR2 drives reactive phenotype of microglia and its inhibition reduces microglia activation and neurotoxic proinflammatory mediators after JEV infection.

Objectives:To examine the clinicopathologic profile of leiomyoma in surgically removed uteri in a rural tertiary care hospital of north India between January 2008 and August 2012.Methods:Fibroids are the most common benign tumors of reproductive-age women, with the genital tract being the most common site for tumors. The type of fibroids and secondary changes were confirmed by histopathologic examination of excised uteri.Results:Of the 200 patients with clinically suspected uterine fibroids, diagnosis was confirmed in 180. An intramural variant was most common (66.7%), followed by the subserosal (22.2%), submucosal (8.9%), and cervical (2.2%) varieties. Menorrhagia, abdominal mass, and abdominal pain were the most common clinical symptoms associated with intramural leiomyoma. Metrorrhagia was observed with submucosal leiomyoma. Secondary changes such as hyaline, mucoid, cystic, and fatty degeneration were also seen, most commonly in intramural leiomyoma.Conclusions:This study examined the clinicopathologic profile of leiomyoma and is being presented on account of its rarity. To the best of the authors’ knowledge, such a study on a rural population of North India has not been done previously. It revealed that intramural leiomyoma was the most common variant and menorrhagia was the prime clinical symptom. Secondary changes such as hyaline, mucoid, cystic, and fatty degeneration were also seen, most commonly in intramural leiomyoma.