Unraveling neuroprotection in Parkinson's disease: Nrf2-Keap1 pathway's vital role amidst pathogenic pathways.

Parkinson's disease (PD) is an age-related chronic neurological condition characterized by progressive degeneration of dopaminergic neurons and the presence of Lewy bodies, primarily composed of alpha-synuclein and ubiquitin. The pathophysiology of PD encompasses alpha-synuclein aggregation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired autophagy and ubiquitin-proteasome systems. Among these, the Keap1-Nrf2 pathway is a key regulator of antioxidant defense mechanisms.

ER calcium depletion as a key driver for impaired ER-to-mitochondria calcium transfer and mitochondrial dysfunction in Wolfram syndrome.

Wolfram syndrome is a rare genetic disease caused by mutations in the WFS1 or CISD2 gene. A primary defect in Wolfram syndrome involves poor ER Ca handling, but how this disturbance leads to the disease is not known. The current study, performed in primary neurons, the most affected and disease-relevant cells, involving both Wolfram syndrome genes, explains how the disturbed ER Ca handling compromises mitochondrial function and affects neuronal health.

Endoplasmic reticulum stress and its role in various neurodegenerative diseases.

The Endoplasmic reticulum (ER), a critical cellular organelle, maintains cellular homeostasis by regulating calcium levels and orchestrating essential functions such as protein synthesis, folding, and lipid production. A pivotal aspect of ER function is its role in protein quality control. When misfolded proteins accumulate within the ER due to factors like protein folding chaperone dysfunction, toxicity, oxidative stress, or inflammation, it triggers the Unfolded protein response (UPR).

Proteomics profiling and in silico analysis of peptides identified during Fusarium oxysporum infection in castor (Ricinus communis).

Castor is industrially important non-edible oil seeds crop severely affected by soil borne pathogen Fusarium oxysporum f. sp. ricini which causes heavy economic losses among the castor growing states in India and worldwide.

Stability estimation through multivariate approach among solasodine-rich lines of (C.B. Clarke): an important industrial plant.

is a medicinally important plant that is a source of steroidal alkaloids 'solasodine.' It has various industrial applications, including oral contraceptives and other pharmaceutical uses. The present study was based on 186 germplasm of , which were analyzed for the stability of economically important traits like solasodine content and fruit yield.

Psychiatric Morbidity: A Retrospective Study From a Tertiary Care Center.

Background It is crucial to monitor the psychiatric morbidity patterns of patients to comprehend the burden and trends of mental illness, as well as to create targeted prevention and intervention strategies. Due to the significant regional differences in mental illness, the current study assessed the psychiatric morbidity pattern from a tertiary care center in Central India. Methods We conducted this retrospective record-based study using data from the outpatient department register of the Psychiatry Department of Government Bundelkhand Medical College, Sagar, Madhya Pradesh, India.

Label-Free Physical-Analytical Techniques Reveal Epigenetic Modifications of Breast Cancer Chromosomes.

Epigenetic dysregulation including DNA methylation and histone modifications is being increasingly recognized as a promising biomarker for the diagnosis and prognosis of cancer. Herein, we devised a label-free analytical toolbox comprising IR, UV-vis, CD spectroscopy, and cyclic voltammetry, which is capable to differentiate significantly hyper-methylated breast cancer chromosomes from the normal breast epithelial counterparts.

Negative feedback system to maintain cell ROS homeostasis: KEAP1-PGAM5 complex senses mitochondrially generated ROS to induce mitophagy.

If cellular reactive oxygen species (ROS) production surpasses the intracellular antioxidant capacity, thus altering the ROS homeostasis, the cell needs to eradicate faulty mitochondria responsible for these excessive ROS. We have shown that even moderate ROS production breaks the KEAP1-PGAM5 complex, inhibiting the proteasomal removal of PGAM5. This leads to an accumulation of PGAM5 interfering with PINK1 processing that sensitizes mitochondria to autophagic removal.

Molecular Mechanisms and Regulation of Mammalian Mitophagy.

Mitochondria in the cell are the center for energy production, essential biomolecule synthesis, and cell fate determination. Moreover, the mitochondrial functional versatility enables cells to adapt to the changes in cellular environment and various stresses. In the process of discharging its cellular duties, mitochondria face multiple types of challenges, such as oxidative stress, protein-related challenges (import, folding, and degradation) and mitochondrial DNA damage.

A novel role of KEAP1/PGAM5 complex: ROS sensor for inducing mitophagy.

When ROS production exceeds the cellular antioxidant capacity, the cell needs to eliminate the defective mitochondria responsible for excessive ROS production. It has been proposed that the removal of these defective mitochondria involves mitophagy, but the mechanism of this regulation remains unclear. Here, we demonstrate that moderate mitochondrial superoxide and hydrogen peroxide production oxidates KEAP1, thus breaking the interaction between this protein and PGAM5, leading to the inhibition of its proteasomal degradation.

Melatonin and oxidative stress in melasma - an unexplored territory; a prospective study.

Background: Melasma, an acquired disorder of hyperpigmentation, is the most common pigmentary disorder in India. Many factors are implicated in the pathogenesis, and recently the role of oxidative damage including melatonin has been postulated. This study was undertaken to evaluate the role of oxidative stress and serum melatonin in pathogenesis of melasma.

Mitochondrial transport proteins RHOT1 and RHOT2 serve as docking sites for PRKN-mediated mitophagy.

The Parkinson disease-associated proteins PINK1 and PRKN coordinate the ubiquitination of mitochondrial outer membrane proteins to tag them either for degradation or for autophagic clearance of the mitochondrion. The proteins include the mitochondrial trafficking proteins RHOT1 and RHOT2, the removal of which may be required for immobilization of mitochondria prior to mitophagy. Here, we demonstrate that RHOT1 and RHOT2 are not only substrates for PINK1-PRKN-dependent degradation but that they also play an active role in the process of mitophagy.

Miro proteins prime mitochondria for Parkin translocation and mitophagy.

The Parkinson's disease-associated protein kinase PINK1 and ubiquitin ligase Parkin coordinate the ubiquitination of mitochondrial proteins, which marks mitochondria for degradation. Miro1, an atypical GTPase involved in mitochondrial trafficking, is one of the substrates tagged by Parkin after mitochondrial damage. Here, we demonstrate that a small pool of Parkin interacts with Miro1 before mitochondrial damage occurs.

Role of oxidative stress in melasma: a prospective study on serum and blood markers of oxidative stress in melasma patients.

Background: Melasma is a common pigmentary disorder presenting in the dermatological clinic. Many factors have been implicated in the pathogenesis, however, the cause still remains elusive. Recently the effect of oxidative damage has been proposed in the etiopathogenesis of melasma.

Role of Mitochondrial Dynamics in Neuronal Development: Mechanism for Wolfram Syndrome.

Deficiency of the protein Wolfram syndrome 1 (WFS1) is associated with multiple neurological and psychiatric abnormalities similar to those observed in pathologies showing alterations in mitochondrial dynamics. The aim of this study was to examine the hypothesis that WFS1 deficiency affects neuronal function via mitochondrial abnormalities. We show that down-regulation of WFS1 in neurons leads to dramatic changes in mitochondrial dynamics (inhibited mitochondrial fusion, altered mitochondrial trafficking, and augmented mitophagy), delaying neuronal development.

Mitochondrial biogenesis is required for axonal growth.

During early development, neurons undergo complex morphological rearrangements to assemble into neuronal circuits and propagate signals. Rapid growth requires a large quantity of building materials, efficient intracellular transport and also a considerable amount of energy. To produce this energy, the neuron should first generate new mitochondria because the pre-existing mitochondria are unlikely to provide a sufficient acceleration in ATP production.

Status and Interrelationship of Zinc, Copper, Iron, Calcium and Selenium in Prostate Cancer.

Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer.

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway.

Neurogenesis involves generation of new neurons through finely tuned multistep processes, such as neural stem cell (NSC) proliferation, migration, differentiation, and integration into existing neuronal circuitry in the dentate gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis is involved in cognitive functions and altered in various neurodegenerative disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizures.

Activation of Autophagic Flux against Xenoestrogen Bisphenol-A-induced Hippocampal Neurodegeneration via AMP kinase (AMPK)/Mammalian Target of Rapamycin (mTOR) Pathways.

The human health hazards related to persisting use of bisphenol-A (BPA) are well documented. BPA-induced neurotoxicity occurs with the generation of oxidative stress, neurodegeneration, and cognitive dysfunctions. However, the cellular and molecular mechanism(s) of the effects of BPA on autophagy and association with oxidative stress and apoptosis are still elusive.

SRD5A2 gene polymorphisms and the risk of benign prostatic hyperplasia but not prostate cancer.

Background: Testosterone, a primary androgen in males, is converted into its most active form, dihydrotestosterone (DHT), by 5α-reductase type 2 (encoded by the SRD5A2 gene) in the prostate. DHT is necessary for prostatic growth and has five times higher binding affinity than testosterone for androgen receptors. We hypothesized that polymorphic variations in the SRD5A2 gene may affect the risk of benign prostatic hyperplasia and prostate cancer.

BECN1 is involved in the initiation of mitophagy: it facilitates PARK2 translocation to mitochondria.

The autophagy protein BECN1/Beclin 1 is known to play a central role in autophagosome formation and maturation. The results presented here demonstrate that BECN1 interacts with the Parkinson disease-related protein PARK2. This interaction does not require PARK2 translocation to mitochondria and occurs mostly in cytosol.