Cytotoxic Effect of Amyloid-β1-42 Oligomers on Endoplasmic Reticulum and Golgi Apparatus Arrangement in SH-SY5Y Neuroblastoma Cells.

Amyloid-β oligomers are a cytotoxic structure that is key for the establishment of the beginning stages of Alzheimer's disease (AD). These structures promote subcellular alterations that cause synaptic dysfunction, loss of cell communication, and even cell death, generating cognitive deficits. The aim of this study was to investigate the cytotoxic effects of amyloid-β1-42 oligomers (AβOs) on the membranous organelles involved in protein processing: the endoplasmic reticulum (ER) and Golgi apparatus (GA).

Correction: Viveros-Paredes et al. Neuroprotective Effects of β-Caryophyllene against Dopaminergic Neuron Injury in a Murine Model of Parkinson's Disease Induced by MPTP. 2017, , 60.

In the original publication [...

JNK signaling and its impact on neural cell maturation and differentiation.

C-Jun-N-terminal-kinases (JNKs), members of the mitogen-activated-protein-kinase family, are significantly linked with neurological and neurodegenerative pathologies and cancer progression. However, JNKs serve key roles under physiological conditions, particularly within the central-nervous-system (CNS), where they are critical in governing neural proliferation and differentiation during both embryogenesis and adult stages. These processes control the development of CNS, avoiding neurodevelopment disorders.

Raman spectroscopy to assess the differentiation of bone marrow mesenchymal stem cells into a glial phenotype.

Background: Mesenchymal stem cells (MSCs) are multipotent precursor cells with the ability to self-renew and differentiate into multiple cell linage, including the Schwann-like fate that promotes regeneration after lesion. Raman spectroscopy provides a precise characterization of the osteogenic, adipogenic, hepatogenic and myogenic differentiation of MSCs. However, the differentiation of bone marrow mesenchymal stem cells (BMSCs) towards a glial phenotype (Schwann-like cells) has not been characterized before using Raman spectroscopy.

Inhibition of VEGFR-2 by SU5416 increases neonatally glutamate-induced neuronal damage in the cerebral motor cortex and hippocampus.

Vascular endothelial growth factor (VEGF) exerts neuroprotective or proinflammatory effects, depending on what VEGF forms (A-E), receptor types (VEGFR1-3), and intracellular signaling pathways are involved. Neonatal monosodium glutamate (MSG) treatment triggers neuronal death by excitotoxicity, which is commonly involved in different neurological disorders, including neurodegenerative diseases. This study was designed to evaluate the effects of VEGFR-2 inhibition on neuronal damage triggered by excitotoxicity in the cerebral motor cortex (CMC) and hippocampus (Hp) after neonatal MSG treatment.

Impact of New Drugs for Therapeutic Intervention in Alzheimer's Disease.

The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed.

Dual and Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells.

(1) Background: The c-Jun-NH2-terminal protein kinase (JNK) is a mitogen-activated protein kinase involved in regulating physiological processes in the central nervous system. However, the dual genetic deletion of and (upstream activators of JNK) in adult mice is not reported. The aim of this study was to induce the genetic deletion of in adult mice and analyze their effect in hippocampal neurogenesis.

Current Evidence on the Protective Effects of Recombinant Human Erythropoietin and Its Molecular Variants against Pathological Hallmarks of Alzheimer's Disease.

Substantial evidence in the literature demonstrates the pleiotropic effects of the administration of recombinant human erythropoietin (rhEPO) and its molecular variants in different tissues and organs, including the brain. Some of these reports suggest that the chemical properties of this molecule by itself or in combination with other agents (e.g.

c-Jun N-Terminal Kinases in Alzheimer's Disease: A Possible Target for the Modulation of the Earliest Alterations.

Given the highly multifactorial origin of Alzheimer's disease (AD) neuropathology, disentangling and orderly knowing mechanisms involved in sporadic onset are arduous. Nevertheless, when the elements involved are dissected into smaller pieces, the task becomes more accessible. This review aimed to describe the link between c-Jun N-terminal Kinases (JNKs), master regulators of many cellular functions, and the early alterations of AD: synaptic loss and dysregulation of neuronal transport.

Involvement of JNK1 in Neuronal Polarization During Brain Development.

The c-Jun N-terminal Kinases (JNKs) are a group of regulatory elements responsible for the control of a wide array of functions within the cell. In the central nervous system (CNS), JNKs are involved in neuronal polarization, starting from the cell division of neural stem cells and ending with their final positioning when migrating and maturing. This review will focus mostly on isoform JNK1, the foremost contributor of total JNK activity in the CNS.

Expression of VEGF- and tight junction-related proteins in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy.

The blood-brain barrier (BBB) maintains the optimal microenvironment for brain function. Tight junctions (TJs) allow endothelial cells to adhere to each other, leading to the formation of a barrier that prevents the penetration of most molecules via transcellular routes. Evidence has indicated that seizure-induced vascular endothelial growth factor (VEGF) type 2 receptor (VEGFR-2) pathway activation weakens TJs, inducing vasodilatation and increasing vascular permeability and subsequent brain injury.

Glutamate induced neonatal excitotoxicity modifies the expression level of EAAT1 (GLAST) and EAAT2 (GLT-1) proteins in various brain regions of the adult rat.

Glutamate-mediated excitatory synaptic signalling is primarily controlled by excitatory amino acid transporters (EAATs), such as EAAT1 and EAAT2, which are located mostly on astrocytes and, together, uptake more than 95 % of extracellular glutamate. Alterations in the functional expression levels of EAATs can lead to excessive extracellular glutamate accumulation, potentially triggering excitotoxicity and seizures, among other neurological disorders. Excitotoxicity induced in early developmental stages can lead to lasting changes in several neurotransmission systems, including the glutamatergic system, which could make the brain more susceptible to a second insult.

Correction to: Peripheral and Central Effects of Memantine in a Mixed Preclinical Mice Model of Obesity and Familial Alzheimer's Disease.

The original version of this article unfortunately contained mistake. The authors found that Fig. 4.

Neonatal excitotoxicity modifies blood-brain barrier properties increasing its susceptibility to hypertonic shock in adulthood.

Early responses to a neurological excitotoxic process include blood-brain barrier (BBB) impairment and overexpression of vascular endothelial growth factor (VEGF), but the long-term effects of excitotoxicity on the BBB properties remain unknown. To assess this, we induced an excitotoxic process on male rats by neonatal monosodium glutamate (MSG) treatment. At postnatal day (PD) 60, we measured the expression level of structural proteins of the BBB and the VEGF type-2 receptor (VEGFR-2) protein in the cerebral motor cortex (CMC), striatum (STR), hippocampus (Hp), entorhinal cortex (Ent), and hypothalamus (Hyp).

New Aspects of VEGF, GABA, and Glutamate Signaling in the Neocortex of Human Temporal Lobe Pharmacoresistant Epilepsy Revealed by RT-qPCR Arrays.

In the epilepsy spectrum, temporal lobe epilepsy (TLE) is the most common and devastating focal and symptomatic epilepsy form in adults, where more than 30% of patients develop pharmacoresistance. It is not fully understood how the gene expression contributes to establishing an epileptic phenotype. Cerebrovascular remodeling directed by VEGF (vascular endothelial growth factor) signaling might modulate the synaptic neurotransmission in the epileptic brain.

Benzodiazepines and Related Drugs as a Risk Factor in Alzheimer's Disease Dementia.

Benzodiazepines (BZDs) and Z-drugs are compounds widely prescribed in medical practice due to their anxiolytic, hypnotic, and muscle relaxant properties. Yet, their chronic use is associated with cases of abuse, dependence, and relapse in many patients. Furthermore, elderly people are susceptible to alterations in pharmacodynamics, pharmacokinetics as well as to drug interaction due to polypharmacy.

Neuroprotective and Neurorestorative Effects of Epo and VEGF: Perspectives for New Therapeutic Approaches to Neurological Diseases.

Background: Erythropoietin (Epo) and vascular endothelial growth factor (VEGF) are two vasoactive molecules with essential trophic effects for brain development. The expression and secretion of both molecules increase in response to neuronal damage and they exert protective and restorative effects, which may also be accompanied by adverse side effects.

Objective: We review the most relevant evidence on the neuroprotective and neurorestorative effects of Epo and VEGF in three of the most frequent neurological disorders, namely, stroke, epilepsy and Alzheimer's disease, to develop new therapeutic approaches.

Role of c-Jun N-Terminal Kinases (JNKs) in Epilepsy and Metabolic Cognitive Impairment.

Previous studies have reported that the regulatory function of the different c-Jun N-terminal kinases isoforms (JNK1, JNK2, and JNK3) play an essential role in neurological disorders, such as epilepsy and metabolic-cognitive alterations. Accordingly, JNKs have emerged as suitable therapeutic strategies. In fact, it has been demonstrated that some unspecific JNK inhibitors exert antidiabetic and neuroprotective effects, albeit they usually show high toxicity or lack therapeutic value.

Epigallocatechin-3-Gallate (EGCG) Improves Cognitive Deficits Aggravated by an Obesogenic Diet Through Modulation of Unfolded Protein Response in APPswe/PS1dE9 Mice.

Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been previously investigated for its neuroprotective effects in vitro and in vivo. In the present study, we aimed to evaluate its possible beneficial effects in a well-established preclinical mixed model of familial Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) based on the use of transgenic APPswe/PS1dE9 (APP/PS1) mice fed with a high fat diet (HFD). C57BL/6 wild-type (WT) and APP/PS1 mice were used in this study.

c-Jun N-terminal Kinase 1 ablation protects against metabolic-induced hippocampal cognitive impairments.

The development of metabolic alterations like insulin resistance has been associated with dysfunctions in mitochondrial oxidative capacity, induction of neuroinflammatory responses, and the appearance of cognitive impairments in the brain. The c-Jun N-terminal Kinase 1 (JNK1) is a potential key modulator of these mechanisms. The current study identifies a protective effect of whole-body JNK1 knockout in the presence of a high-fat diet (HFD).

β-Caryophyllene Reduces DNA Oxidation and the Overexpression of Glial Fibrillary Acidic Protein in the Prefrontal Cortex and Hippocampus of d-Galactose-Induced Aged BALB/c Mice.

Aging is associated with detrimental cellular and cognitive changes, making it an important public health concern; yet, many of these changes may be influenced by nutritional interventions. The natural sesquiterpene β-caryophyllene (BCP) has anti-inflammatory and antioxidant effects that are mediated by cannabinoid type-2 receptor activation, and these actions promote neuroprotection in different animal models that involve a cognitive damage. Consequently, whether chronic administration of BCP might prevent the age-related cellular and cognitive damage in a model of aging induced by chronic d-galactose (GAL) consumption was assessed here.

The Involvement of Peripheral and Brain Insulin Resistance in Late Onset Alzheimer's Dementia.

Nowadays, Alzheimer's disease (AD) is a severe sociological and clinical problem. Since it was first described, there has been a constant increase in its incidence and, for now, there are no effective treatments since current approved medications have only shown short-term symptomatic benefits. Therefore, it is imperative to increase efforts in the search for molecules and non-pharmacological strategies that are capable of slowing or stopping the progress of the disease and, ideally, to reverse it.