BACE1-dependent metabolism of neuregulin 1: Bridging the gap in explaining the occurrence of schizophrenia-like symptoms in Alzheimer's disease with psychosis?

Alzheimer's disease is a neurodegenerative disease mainly characterized by cortico-neuronal atrophy, impaired memory and other cognitive declines. On the other hand, schizophrenia is a neuro-developmental disorder with an overtly active central nervous system pruning system resulting into abrupt connections with common symptoms including disorganised thoughts, hallucination and delusion. Nevertheless, the fronto-temporal anomaly presents itself as a common denominator for the two pathologies.

Post-treatment symptomatic improvement of the eastern Indian ADHD probands is influenced by genetic variations.

Objectives: Symptomatic remediation from attention deficit hyperactivity disorder (ADHD)-associated traits is achieved by treatment with methylphenidate (MPH)/atomoxetine (ATX). We have analyzed the association of functional variations, rs1065852, rs3892097, rs1135840, and rs1058164, with ADHD in the Indian subjects.

Methods: Subjects were recruited following the Diagnostic and Statistical Manual for Mental Disorders.

Cdk5-p25 as a key element linking amyloid and tau pathologies in Alzheimer's disease: Mechanisms and possible therapeutic interventions.

Despite the fact that the small atypical serine/threonine cyclin-dependent kinase 5 (Cdk5) is expressed in a number of tissues, its activity is restricted to the central nervous system due to the neuron-only localization of its activators p35 and p39. Although its importance for the proper development and function of the brain and its role as a switch between neuronal survival and death are unmistakable and unquestionable, Cdk5 is nevertheless increasingly emerging, as supported by a large number of publications on the subject, as a therapeutic target of choice in the fight against Alzheimer's disease. Thus, its aberrant over activation via the calpain-dependent conversion of p35 into p25 is observed during the pathogenesis of the disease where it leads to the hyperphosphorylation of the β-amyloid precursor protein and tau.

Specific dopaminergic genetic variants influence impulsivity, cognitive deficit, and disease severity of Indian ADHD probands.

Background: Impulsivity (Imp), being one of the cardinal symptoms of Attention Deficit Hyperactivity Disorder (ADHD), often leads to inappropriate responses to stimuli. Since the dopaminergic system is the primary target for pharmaceutical intervention in ADHD, we investigated the association between ADHD-related Imp and functional gene variants of the dopamine transporter (SLC6A3) and catechol-O-methyltransferase involved in dopamine clearance.

Methods And Results: Indo-Caucasoid families with ADHD probands (N = 217) were recruited based on the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Synthesis and Characterization of Andrographolide Derivatives as Regulators of βAPP Processing in Human Cells.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder, one of the main characteristics of which is the abnormal accumulation of amyloid peptide (Aβ) in the brain. Whereas β-secretase supports Aβ formation along the amyloidogenic processing of the β-amyloid precursor protein (βAPP), α-secretase counterbalances this pathway by both preventing Aβ production and triggering the release of the neuroprotective sAPPα metabolite. Therefore, stimulating α-secretase and/or inhibiting β-secretase can be considered a promising anti-AD therapeutic track.

Phenanthroline impairs βAPP processing and expression, increases p53 protein levels and induces cell cycle arrest in human neuroblastoma cells.

Mis-functional βAPP processing is deemed to be the major phenomenon resulting in increased neuronal cell death, impaired neurogenesis and the loss of synapses, which eventually manifest as the complex symptoms of Alzheimer's disease. Despite of several milestones having been achieved in the field of drug development, the stigma of the disorder as an incurable disease still remains. Some ADAM proteases mediate the physiological non-amyloidogenic α-secretase processing of βAPP that generates neuroprotective sAPPα production.

Folate System Gene Variant rs1801394 66A>G may have a Causal Role in Down Syndrome in the Eastern Indian Population.

Down syndrome (DS) is associated with trisomy of the 21 chromosome in more than 95% cases. The extra chromosome mostly derives due to abnormal chromosomal segregation, i.e.

Dopaminergic gene analysis indicates influence of inattention but not IQ in executive dysfunction of Indian ADHD probands.

Organizational inefficiency and inattention are speculated to be the reason for executive deficit (ED) of ADHD probands. Even with average IQ, probands often perform poorly due to higher inattention. Pharmacotherapy, cognitive behavioural therapy, and counselling provide only symptomatic relief.

Parental age and developmental milestones: pilot study indicated a role in understanding ADHD severity in Indian probands.

Background: In different ethnic groups, birth related factors have shown significant influence in the etiology of Attention deficit hyperactivity disorder (ADHD). Based on these interesting findings, we aimed to investigate association between different pre- and post natal variables and ADHD associated traits in Indian subjects.

Methods: ADHD Probands recruited based on the DSM-IV, were assessed by the Conner's Parent Rating Scale for behavioral problem (BPr), inattention (IA), hyperactivity (HA) and ADHD index (AI).

Methamphetamine regulates βAPP processing in human neuroblastoma cells.

Methamphetamine is a potent and highly addictive psychostimulant whose abuse has turned out to be a global health hazard. The multitudinous effects it exerts at the cellular level induces neurotoxic responses in the human brain, ultimately leading to neurocognitive disorders. Strikingly, brain changes, tissue damage and neuropsychological symptoms due to Meth exposure compels and necessitates to link the probability of risk of developing premature Alzheimer's disease, a progressive neurodegenerative disorder characterized by amyloid plaques composed of amyloid-β peptides and clinical dementia.

Pilot study indicate role of preferentially transmitted monoamine oxidase gene variants in behavioral problems of male ADHD probands.

Background: Attention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Symptom severity varies widely and boys are diagnosed more frequently than girls. ADHD probands were reported to have abnormal transmissions of dopamine, serotonin, and/or noradrenaline.

Cyclin-dependent Kinase 5: Novel role of gene variants identified in ADHD.

Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers.

Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal.

Background: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention, excessive motor activity and impulsivity detected mostly during childhood. These traits are known to be controlled by monoamine neurotransmitters, chiefly dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA) and B (MAOB), two isoenzymes bound to the outer membrane of mitochondria, are involved in the degradation of monoamines and were explored for association with ADHD in different ethnic groups.

The Dopamine Receptor D5 May Influence Age of Onset: An Exploratory Study on Indo-Caucasoid ADHD Subjects.

The objective was to investigate contribution of the dopamine receptor 5 (DRD5) gene variants in the symptoms of attention-deficit/hyperactivity disorder (ADHD) probands since brain regions identified to be affected in these group of patients have higher expression of the DRD5 receptor. Out of 22 exonic variants, 19 were monomorphic in the Indo-Caucasoid individuals. rs6283 "C" and rs113828117 "A" exhibited significant higher occurrence in families with ADHD probands.

Potential contribution of dopaminergic gene variants in ADHD core traits and co-morbidity: a study on eastern Indian probands.

Association of dopaminergic genes, mainly receptors and transporters, with Attention Deficit Hyperactivity Disorder (ADHD) has been investigated throughout the world due to the importance of dopamine (DA) in various physiological functions including attention, cognition and motor activity, traits. However, till date, etiology of ADHD remains unknown. We explored association of functional variants in the DA receptor 2 (rs1799732 and rs6278), receptor 4 (exon 3 VNTR and rs914655), and transporter (rs28363170 and rs3836790) with hyperactivity, cognitive deficit, and co-morbid disorders in eastern Indian probands.