IGF1R/ARRB1 Mediated Regulation of ERK and cAMP Pathways in Response to Aβ Unfolds Novel Therapeutic Avenue in Alzheimer's Disease.

IGF1R/INSR signaling is crucial for understanding Alzheimer's disease (AD) and may aid in the development of potent therapeutic strategies. This study investigated the expression and activity of these receptors and their potential to form functional hybrids in response to amyloid beta (Aβ). IGF1R, INSR, and ARRB1 were found to be upregulated in AD.

Small RNA sequencing of differentiated astrocytoma exposed to NMOSD patient sera reveals perturbations in neurodegenerative signaling.

The signaling pathways behind severe astrocytic lysis with Aquaporin4 auto-antibody (AQP4-IgG) seropositivity, and reactive astrocytosis with myelin oligodendrocyte glycoprotein auto-antibody (MOG-IgG) seropositivity, remain largely unexplored in Neuromyelitis optica spectrum disorder (NMOSD), while almost no molecular details being known about double-seronegative (DN) patients. Recent discovery of glial fibrillary acidic protein (GFAP) in DN NMOSD patients' cerebrospinal fluid, akin to AQP4-IgG + ve cases, suggests astrocytopathy. Here, we aim to study small non coding RNA (sncRNA) signature alterations in astrocytes exposed to AQP4-IgG + ve and MOG-IgG + ve patient sera, and their potential resemblance with DN-NMOSD.

A Holistic Analysis of Alzheimer's Disease-Associated lncRNA Communities Reveals Enhanced lncRNA-miRNA-RBP Regulatory Triad Formation Within Functionally Segregated Clusters.

Recent studies on the regulatory networks implicated in Alzheimer's disease (AD) evince long non-coding RNAs (lncRNAs) as crucial regulatory players, albeit a poor understanding of the mechanism. Analyzing differential gene expression in the RNA-seq data from the post-mortem AD brain hippocampus, we categorized a list of AD-dysregulated lncRNA transcripts into functionally similar communities based on their k-mer profiles. Using machine-learning-based algorithms, their subcellular localizations were mapped.

The receptor tyrosine kinase IGF1R and its associated GPCRs are co-regulated by the noncoding RNA NEAT1 in Alzheimer's disease.

The study is based on the complexity of Insulin like growth factor receptor (IGF1R) signaling and its regulation by noncoding RNAs (ncRNAs). IGF1R signaling is an important cascade in Alzheimer's disease (AD); however, its regulation and roles are poorly understood. Due to the presence of β-arrestin and GPCR Receptor Kinase binding sites, this protein has been termed a 'functional hybrid', as it can take part in both kinase and GPCR signaling pathways, further adding to its complexity.

Imaging and Assay of the Dynamics of Cytotoxic Huntingtin (HTT) Protein Aggregates Regulated by lncRNAs.

Huntington's disease (HD) pathogenesis involves deregulation of coding and noncoding RNA transcripts of which the involvement of long noncoding RNAs (lncRNA) has been realized recently. Of these, Meg3, Neat1, and Xist showed a consistent and significant increase in HD cell and animal models. In the present study, we formulate a methodology to visualize and quantify intracellular aggregates formed by mutant HTT protein.

Quantitative Investigation of Neuroprotective Role of ROR1 in a Cell Culture Model of Alzheimer's Disease.

Cytoskeletal and microtubule atrophy are major hallmarks of Alzheimer's disease (AD). A method to investigate endogenous proteins that can interact/stabilize the cytoskeleton (under pathological cues) is rare. Here, we describe how receptor tyrosine kinase-like orphan receptor 1 (ROR1), a receptor tyrosine kinase (RTK), can act as a neuroprotective molecule by promoting neurite outgrowth, stabilizing cytoskeletal components, and altering the dynamics of actin assembly in a cell culture model of AD.

Cell-Based Assay to Detect the Autoantibody Serostatus in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).

Cell-based assay (CBA) is an immunofluorescence assay that is extensively used for the confirmatory diagnosis of inflammatory demyelinating diseases of the central nervous system, like neuromyelitis optica spectrum disorder (NMOSD). Detecting the type of autoantibody present in the sera of the patients is the primary goal. CBA is the most sensitive and recommended detection method among all similar tools.

Long non-coding RNA MALAT1 protects against Aβ induced toxicity by regulating the expression of receptor tyrosine kinase EPHA2 via quenching miR-200a/26a/26b in Alzheimer's disease.

Altered expressions of Receptor Tyrosine Kinases (RTK) and non-coding (nc) RNAs are known to regulate the pathophysiology of Alzheimer's disease (AD). However, specific understanding of the roles played, especially the mechanistic and functional roles, by long ncRNAs in AD is still elusive. Using mouse tissue qPCR assays we observe changes in the expression levels of 41 lncRNAs in AD mice of which only 7 genes happen to have both human orthologs and AD associations.

Dynamics of AQP4 upon exposure to seropositive patient serum before and after Rituximab therapy in Neuromyelitis Optica: A cell-based study.

Neuromyelitis Optica (NMO) is an autoimmune inflammatory disease that affects the optic nerves and spinal cord. The autoantibody is generated against the abundant water channel protein of the brain, Aquaporin 4 (AQP4). Of the two isoforms of AQP4, the shorter one (M23) often exists as a supramolecular assembly known as an orthogonal array of particles (OAPs).

A nexus of miR-1271, PAX4 and ALK/RYK influences the cytoskeletal architectures in Alzheimer's Disease and Type 2 Diabetes.

Alzheimer's Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Reportedly, two non-canonical Receptor Tyrosine Kinases (RTKs), ALK and RYK, both targets of the same micro RNA miR-1271, exhibit significant and consistent functional down-regulation in post-mortem AD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor.

Impact of porous nanomaterials on inhibiting protein aggregation behaviour.

Aggregation of intrinsically disordered as well as the ordered proteins under certain premises or physiological conditions leads to pathological disorder. Here we have presented a detailed investigation on the effect of a porous metallic (Au) and a non-metallic (Si) nanomaterial on the formation of ordered (fiber-like/amyloid) and disordered (amorphous) aggregates of proteins. Porous nanogold (PNG) was found to reduce the amyloid aggregation of insulin but does not have much impact on the lag phase in the aggregation kinetics, whereas porous nano-silica (PNS) was found both to decrease the amount of aggregation as well as prolong the lag phase of amyloid fiber formation from insulin.

LncRNA Xist, X-chromosome Instability and Alzheimer's Disease.

Neurodegenerative Diseases (NDD) are the major contributors to age-related causes of mental disability on a global scale. Most NDDs, like Alzheimer's Disease (AD), are complex in nature - implying that they are multi-parametric both in terms of heterogeneous clinical outcomes and underlying molecular paradigms. Emerging evidence from high throughput genomic, transcriptomic and small RNA sequencing experiments hint at the roles of long non-coding RNAs (lncRNAs) in AD.

E2F1 activates MFN2 expression by binding to the promoter and decreases mitochondrial fission and mitophagy in HeLa cells.

Mitofusin-2 (MFN2) is primarily involved in mitochondrial fusion and participates in diverse biological processes. Several reports show that MFN2 is a target of different miRNAs; however, the transcriptional regulation of MFN2 has not been extensively studied. To gain insight into the transcriptional regulation of MFN2, we expressed E2F transcription factor 1 (E2F1) exogenously and observed that it increased the endogenous expression of MFN2 by binding to its putative promoter region.

In vitro degradation of β-amyloid fibrils by microbial keratinase.

Introduction: Amyloid fibrils are misfolded, protease-resistant forms of normal proteins. They are infectious such as prions or noninfectious such as β-amyloid (Aβ) fibrils causing Alzheimer's disease (AD). Prions and amyloids are structurally similar, possessing cross β-pleated sheet-like structures.

Receptor tyrosine kinases (RTKs) consociate in regulatory clusters in Alzheimer's disease and type 2 diabetes.

Alzheimer's disease (AD) and type 2 diabetes (T2D) share the common hallmark of insulin resistance. It is conjectured that receptor tyrosine kinases (RTKs) play definitive roles in the process. To decipher the signaling overlap behind this phenotypic resemblance, the activity status of RTKs is probed in post-mortem AD and T2D tissues and cell models.

Altered Levels of Long NcRNAs Meg3 and Neat1 in Cell And Animal Models Of Huntington's Disease.

Altered expression levels of protein-coding genes and microRNAs have been implicated in the pathogenesis of Huntington's disease (HD). The involvement of other ncRNAs, especially long ncRNAs (lncRNA), is being realized recently and the related knowledge is still rudimentary. Using small RNA sequencing and PCR arrays we observed perturbations in the levels of 12 ncRNAs in HD mouse brain, eight of which had human homologs.

Systemic study of a natural feedback loop in Huntington's disease at the onset of neurodegeneration.

Aggregation prone Huntingtin (Htt) protein and its aberrations, causing protein misfolding, have been the prototype of intense research for several decades. Misfolded aggregates or oligomers of different sizes not only deregulate the homeostasis, cellular machinery also counterbalances the effects at least at the initial stages, till the balance tilts towards toxicity and degeneration. In this paper, we combine experimental approaches with system based computational modeling to decipher the molecular mechanisms as well as the hidden dynamics leading to neuronal death in HD.

Increased expression of ApoA1 after neuronal injury may be beneficial for healing.

ApoA1 is a player in reverse cholesterol transport that initiates multiple cellular pathways on binding to its receptor ABCA1. Its relation to neuronal injury is however unclear. We found ApoA1 to be increasingly abundant at a later time point in the secondary phase of traumatic spinal cord injury.

Clinical proteomics of enervated neurons.

The dynamic field of neurosciences entails ever increasing search for molecular mechanisms of disease states, especially in the domain of neurodegenerative disorders. The previous century heralded the techniques in proteomics when indexing of the human proteomes relating to various disease conditions became important. Early stage research in certain diseases or pathological conditions requires a more holistic approach of first discovering the proteins of interest for the condition.

Possible role of apolipoprotein A1 in healing and cell death after neuronal injury.

Limited axonal regeneration after traumatic injuries to the CNS presents a challenge in neuroscience. Investigation of CSF from subjects with spinal cord injury (SCI) has found that the lipid catabolism pathway is implicated in the post injury scenario. Sequestration of the CNS by the blood brain barrier ensures a mechanism of cholesterol metabolism and recycling distinct from that in the peripheral tissues.

Chaperone-like protein HYPK and its interacting partners augment autophagy.

To decipher the function(s) of HYPK, a huntingtin (HTT)-interacting protein with chaperone-like activity, we had previously identified 36 novel interacting partners of HYPK. Another 13 proteins were known earlier to be associated with HYPK. On the basis of analysis of the interacting partners of HYPK, it has been shown that HYPK may participate in diverse cellular functions relevant to Huntington's disease.

Regulation of mitochondrial morphology and cell cycle by microRNA-214 targeting Mitofusin2.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the increase in CAG repeats beyond 36 at the exon1 of the gene Huntingtin (HTT). Among the various dysfunctions of biological processes in HD, transcription deregulation due to abnormalities in actions of transcription factors has been considered to be one of the important pathological conditions. In addition, deregulation of microRNA (miRNA) expression has been described in HD.

CSF proteomics of secondary phase spinal cord injury in human subjects: perturbed molecular pathways post injury.

Recovery of sensory and motor functions following traumatic spinal cord injury (SCI) is dependent on injury severity. Here we identified 49 proteins from cerebrospinal fluid (CSF) of SCI patients, eight of which were differentially abundant among two severity groups of SCI. It was observed that the abundance profiles of these proteins change over a time period of days to months post SCI.