Cdc25A phosphatase is activated and mediates neuronal cell death by PUMA via pRb/E2F1 pathway in a model of Parkinson's disease.

Parkinson's disease (PD) is a predominant movement disorder caused mainly due to selective loss of the dopaminergic neurons in the substantia nigra pars compacta of the mid brain. There is currently no cure for PD barring treatments to manage symptoms. The reasons might be due to lack of precise understanding of molecular mechanisms leading to neurodegeneration.

Small-Molecule Cdc25A Inhibitors Protect Neuronal Cells from Death Evoked by NGF Deprivation and 6-Hydroxydopamine.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases that are presently incurable. There have been reports of aberrant activation of cell cycle pathways in neurodegenerative diseases. Previously, we have found that Cdc25A is activated in models of neurodegenerative diseases, including AD and PD.

Predictors and Pathway of Maternal Near Miss: A Case-Control Study in a Tertiary Care Facility in Kolkata.

Background: Use of maternal near-miss (MNM) cases as an adjunct has been advocated to understand the processes of obstetric care because they share similar pathways as maternal deaths. Identifying the predictors and care pathway is crucial to improve the quality of care and end preventable maternal deaths.

Materials And Methods: This case-control study was conducted at a tertiary care facility in Kolkata from May 2019 to March 2020.

Brain-enriched miR-128: Reduced in exosomes from Parkinson's patient plasma, improves synaptic integrity, and prevents 6-OHDA mediated neuronal apoptosis.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the death of mid-brain dopaminergic neurons. Unfortunately, no effective cure or diagnostic biomarkers for PD are available yet. To address this, the present study focuses on brain-enriched small non-coding regulatory RNAs called microRNAs (miRNAs) that are released into the circulation packaged inside small extracellular vesicles called exosomes.

Medha Plus - A novel polyherbal formulation ameliorates cognitive behaviors and disease pathology in models of Alzheimer's disease.

Alzheimer's disease (AD) is a multi-faceted neurodegenerative disorder that leads to drastic cognitive impairments culminating in death. Pathologically, it is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles and neurodegeneration in brain. Complete cure of AD remains elusive to date.

ICAM-1 protects neurons against Amyloid-β and improves cognitive behaviors in 5xFAD mice by inhibiting NF-κB.

Alzheimer's disease (AD) is mainly characterized by amyloid beta (Aβ) plaque deposition and neurofibrillary tangle formation due to tau hyperphosphorylation. It has been shown that astrocytes respond to these pathologies very early and exert either beneficial or deleterious effects towards neurons. Here, we identified soluble intercellular adhesion molecule-1 (ICAM-1) which is rapidly increased in astrocyte conditioned medium derived from Aβ treated cultured astrocytes (Aβ-ACM).

BH3-only proteins Puma and Beclin1 regulate autophagic death in neurons in response to Amyloid-β.

Alzheimer's disease (AD) is characterized by accumulation of senile amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles causing progressive loss of synapse and neuronal death. Out of the various neuron death modalities, autophagy and apoptosis are reported to be the major death paradigms in AD. However, how these two processes lead to neuronal loss is still inconspicuous.

Rheb-mTOR activation rescues Aβ-induced cognitive impairment and memory function by restoring miR-146 activity in glial cells.

Deposition of amyloid beta plaques in adult rat or human brain is associated with increased production of proinflammatory cytokines by associated glial cells that are responsible for degeneration of the diseased tissue. The expression of these cytokines is usually under check and is controlled at the post-transcriptional level via several microRNAs. Computational analysis of gene expression profiles of cortical regions of Alzheimer's disease patients' brain suggests ineffective target cytokine mRNA suppression by existing micro-ribonucleoproteins (miRNPs) in diseased brain.

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.

Astrocyte subtype-specific approach to Alzheimer's disease treatment.

Astrocytes respond to any pathological condition in the central nervous system (CNS) including Alzheimer's disease (AD), and this response is called astrocyte reactivity. Astrocyte reaction to a CNS insult is a highly heterogeneous phenomenon in which the astrocytes undergo a set of morphological, molecular and functional changes with a characteristic secretome profile. Such astrocytes are termed as 'reactive astrocytes'.

Small Non-coding RNAs: Do They Encode Answers for Controlling SARS-CoV-2 in the Future?

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus responsible for the current COVID-19 (coronavirus disease 2019) pandemic, which has hit the world since December 2019. It has spread to about 216 countries worldwide, affecting more than 21.7 million people so far.

Modulation of α-Synuclein Fibrillation by Ultrasmall and Biocompatible Gold Nanoclusters.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, the pathogenesis of which is closely linked to the misfolding and aggregation of the neuronal protein α-Synuclein (A-Syn). Numerous molecules that inhibit/modulate the pathogenic aggregation of A-Syn in an effort to tackle PD pathogenesis have been reported, but none so far have been successful in treating the disease at the clinic. One major reason for this is the poor blood-brain barrier (BBB) permeability of most of the molecules being used.

P38K and JNK pathways are induced by amyloid-β in astrocyte: Implication of MAPK pathways in astrogliosis in Alzheimer's disease.

Astrocyte activation is one of the crucial hallmarks of Alzheimer's disease (AD) along with amyloid-β (Aβ) plaques, neurofibrillary tangles and neuron death. Glial scar and factors secreted from activated astrocytes have important contribution on neuronal health in AD. In this study, we investigated the mechanisms of astrocyte activation both in in vitro and in vivo models of AD.

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.

Human placental laminin: Role in neuronal differentiation, cell adhesion and proliferation.

Human placental extract has wound healing potential. Immuno-blots revealed presence of laminin in placental extract (70 +/- 0.257 μg/ml; n=3).

Trimester-Specific Reference Intervals for Thyroid Function Parameters in Indian Pregnant Women during Final Phase of Transition to Iodine Sufficiency.

Background: Interpretation of thyroid function tests during pregnancy depends on gestational age, method, and population-specific reference intervals. Therefore, there is a worldwide trend to establish trimester-specific levels for different populations. The aim of this study was to establish a trimester-specific reference range for thyroid function parameters during pregnancy in Indian women.

Neuroinvasive potential of a primary respiratory pathogen SARS- CoV2: Summarizing the evidences.

Backround And Aims: After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in SARS-CoV-2 pandemic with unfathomable global responses. The characteristic clinical symptoms for Coronavirus (COVID-19) affected patients are high fever, dry-cough, dyspnoea, lethal pneumonia whereas some patients also show additional neurological signs such as headache, nausea, vomiting etc. The accumulative evidences suggest that SARS-CoV-2 is not only confined within the respiratory tract but may also invade the central nervous system (CNS) and peripheral nervous system (PNS) inducing some fatal neurological diseases.

TIMP-1: A key cytokine released from activated astrocytes protects neurons and ameliorates cognitive behaviours in a rodent model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by two pathologic species, extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles. Astrocytes that maintain normal homeostasis in the brain undergo a set of molecular, cellular and functional changes called reactive astrogliosis in various neurological diseases including AD. It is hypothesized that reactive astrocytes initially tend to protect neurons by reducing Aβ load and by secreting a plethora of cytokines, however, their functions have only been poorly investigated.

Forkhead Box O3a requires BAF57, a subunit of chromatin remodeler SWI/SNF complex for induction of p53 up-regulated modulator of apoptosis (Puma) in a model of Parkinson's disease.

Parkinson's disease (PD) results from the selective loss of dopaminergic neurons of substantia nigra pars compacta region of the midbrain. It has been reported that the transcription factor forkhead Box O3a (FoxO3a) is activated and induces pro-apoptotic protein such as Bcl-2-interacting mediator of cell death (BIM) and p53 up-regulated modulator of apoptosis (PUMA) in variety of neuron death paradigms. Activity of FoxO3a is governed by its post-translational modifications which control its subcellular localization.

Glutamate treatment mimics LTP- and LTD-like biochemical activity in viable synaptosome preparation.

Long-term potentiation (LTP) and long-term depression (LTD) are considered to be the cellular mechanisms behind the increase or decrease of synaptic strength respectively. Electrophysiologically induced LTP/LTD is associated with the activation of glutamate receptors in the synaptic terminals resulting in the initiation of biochemical processes in the postsynaptic terminals and thus propagation of synaptic activity. Isolated nerve endings i.

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.

Multifunctional transcriptional coactivator PC4 is a global co-regulator of p53-dependent stress response and gene regulation.

Human positive coactivator 4 (PC4), a multifunctional chromatin-associated protein, is known to directly interact with p53 and modulate expressions of a few p53-dependent genes. However, the role of PC4 in p53's myriad of other regulatory functions is not known. The p53-PC4 interaction was selectively perturbed by a small peptide which led to abrogation of genotoxic stress-induced up-regulation of many p53-dependent genes and reduction of apoptosis in A549 cells.

RNAi-Mediated Silencing of FOXO Factors.

RNAi-mediated silencing of a particular gene is an important tool in the field of biology. Knocking down experiments has revealed the role of different proteins and their downstream targets. Here, we describe the procedure of silencing transcription factor of Forkhead box class "O" (FOXO) using shRNA.