Neuroprotection

Neurotrophins (NGF, BDNF, NT-3) are endogenous growth factors that exert neuroprotective effects by preventing neuronal death and promoting neurogenesis. They act by binding to their respective high-affinity, pro-survival receptors TrkA, TrkB or TrkC, as well as to p75NTR death receptor. While these molecules have been shown to significantly slow or prevent neurodegeneration, their reduced bioavailability and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic

Prolonged reduction in blood flow leads to stroke, a devastating neurological insult leading cause of adult disability worldwide. One of the early features of stroke is the disruption of neuronal activity that results from the reduction of metabolic supply. Changes in oscillatory brain patterns have been observed in several neurological disorders, including stroke. Evoked neural oscillations in the gamma range have recently shown the ability to restore and maintain intrinsic homeostatic processes in the brain. However, the causal relationship between stimulation and restoration of function is

Stroke is a leading cause of long-term disability worldwide with substantial economic costs. Hence, there is an urge for finding novel therapies to treat disability associated to stroke. This is the main reason research has focused on the discovery of key molecules involved in the functional prognosis of patients after stroke. Adenosine A2A and CB2 are receptors that have proven to be a new therapeutic target to consider in treatment of stroke. A common feature of these receptors in neurons is that their expression is upregulated in neuroinflammation process. On the one hand CB2R show a neurop

…are widely recognized as mediators of neuroprotection from various insults. Recent research has highlighted the distinction between nuclear and non-nuclear ER activation mechanisms, positioning non-nuclear ERs as a safer option, devoid of the cardiovascular and cancer risks associated with nuclear ER activation. In this study, we aimed to confirm the neuroprotective potential of PaPE-1, a novel compound that preferentially activates non-nuc

The plasma membrane is characterized by an asymmetric distribution of phospholipids, maintained by three enzyme classes: flippases, floppases, and scramblases. Phosphatidylserine (PS) is confined to the inner leaflet of the plasma membrane under normal conditions, and its externalization has been linked to both apoptotic and non-apoptotic processes within the central nervous system (CNS). Further, neuronal PS exposure can be transient in stressed but viable cells. Thus, interference with PS-triggered phagocytosis of neurons has been suggested to be beneficial in CNS disorders. The mechanism of

Parkinson’s Disease (PD) is a neurodegenerative disorder associated with the loss of dopaminergic neurons in the nigrostriatal circuit, and the development of motor and non-motor symptoms. Currently, no disease-modifying pharmacological treatments are available, and dopamine-based therapies help to mitigate symptoms but also cause side-effects. In this context, indirect evidence has suggested that activation of metabotropic Glutamate Receptor 3 (mGluR3) exerts neuroprotective effects in animal models of PD. However, the lack of selective agonists/ligands for this receptor has hindered more in-

…MgSO4 may optimize and prolong this neuroprotection in p

…Overexpression of VEGF is involved in neuroprotection and delayed neurodegeneration of MNs. We have previously described a higher amount of VEGF in the extraocular neurons in control adult rats. The objective of this study in the murine SOD1G93A A

…molecular mechanisms underlying DAD9's neuroprotection.Methods: Characterization of α-Synuclein (α-Syn) oligomeric species was performed using ThT fluorescence, SDS-PAGE, DLS, and microscopy. Cell culture assays measured viability, cytotoxicity, and intracellular seeding in transgenic cell models. In vivo experiments were conducted in transgenic C. elegans.Results: T

…activity, with evidence of significant neuroprotection in a neonatal HI mouse model. However, curcumin has limited therapeutic usage due to poor bioavailability and aqueous insolubility. This study aimed to: i) compare free synthetic vs natural curcumi

In multiple sclerosis (MS), oligodendrocyte (OL) degeneration and subsequent demyelination in the central nervous system (CNS) causes neurological impairment. Monocarboxylate transporter 8 (MCT8) may promote OL maturation and myelination by actively transporting thyroid hormone (TH) into the CNS and thereby facilitating key transcription and metabolomic pathways for myelin biogenesis. Diiodothyropropionic acid (DITPA), a synthetic TH-analog, can be transported into the CNS, independent of MCT8 and may promote OL maturation and myelination. In this study, we investigated the potential of DITPA

Quercetin is a polyphenolic flavonoid compound with a proven wide range of biological activities including neuroprotective effects in neuronal injury/neurodegenerative disease models which is related with its high antioxidant properties. However, due to its low water-solubility, poor bioavailability, rapid clearance, instability, and inability to cross the blood–brain barrier (BBB) its potential application for treatment of central nervous system (CNS) disease is limited. Tetrahydroisoquinoline (THIQ) scaffold appears in many drugs’ structures applied in diverse medical applications. Recent re

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by midbrain dopaminergic neuron degeneration and intracellular a-synuclein (aSyn) accumulation. Here we show that AAV-shRNA-mediated inhibition of HDAC5 protected against aSyn-induced neurodegeneration in vitro and in vivo. We also show that AAV-mediated overexpression of aSyn induces HDAC5 nuclear accumulation in dopaminergic neurons in the rat substantia nigra in vivo, and in SH-SY5Y cells in vitro. To investigate the nuclear HDAC5 complex induced by aSyn, we used a co-immunoprecipitation proteomics approach t

Astrocytes are rapidly gaining ground as important regulators and potential therapeutic targets in neurodegeneration. Here, we used the cuprizone model of multiple sclerosis to explore the phenotypic signature of astrocytes in the cortex of mice during early demyelination at week 3 (CPZ3), a timepoint of initial demyelination and glia cell activation. Confocal imaging combined with detailed cell-morphometric analysis of cortical astrocytes after 3-dimensional cell reconstruction revealed the morphological phenotype of astrocytes in early demyelination, characterized by thick and long processes

…of cannabidiol (CBD) result from neuroprotection asssumed to be mainly due to targeting a variety of neuronal receptors. The results of this article first show that CBD protects both primary neurons and primary glia against death induced by glucose and oxygen deprivation. Second, the expression of glial markers in an animal model of neonatal hypoxia-ischemia treated with vehicle or CBD shows that the cannabinoid was able to skew microglia towards a neuroprotective

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Neuronal cells, once impaired, do not undergo spontaneous regeneration; consequently, the disease persists beyond the onset of symptoms. There is a growing recognition of the need for treatments that could protect neurons and potentially modify the disease course because current PD treatments primarily address symptoms without halting the disease progression. Autophagy, a cellular process clearing damaged organelles and proteins, has emerged as a poten

…of LF to the dams enhances the neuroprotection caused by HT following experimental HI. Methods: Pregnant Wistar rats were fed with bovine LF-supplemented diet (1mg/kg) or Control diet from P6 to

Alzheimer’s disease (AD) is a complex disorder involving multiple genetic and non-genetic factors leading to cognitive decline and the accumulation of protein aggregates. Recently, we found that the epi-genetic regulation of Peptidase M20 Domain Containing 1 (PM20D1) modulates AD risk in humans and disease progression in mice through a still unknown mechanism. PM20D1 is an enzyme that facilitates the conjugation of N-acyl amino acids (NAAAs). However, whether NAAAs exert similar protective effects in AD remains unknown. To investigate this hypothesis, we NAAA-treated a series of AD models, and

…signaling is pivotal for neuroprotection, and its impairment during hypoxia/ischemia may increase the risk of cerebral infarction. Our goal was to selectively activate non-nuclear estrogen receptors signaling, providing a wide therapeutic window and minimizing adverse hormonal effects associat

We recently identified Protein kinase N1 (PKN1) as a negative regulator of neuronal AKT activity during postnatal cerebral development. Given the pivotal role of the AKT pro-survival signalling cascade in ischemia/reperfusion, our investigation aimed to determine whether PKN1-mediated AKT inhibition remains relevant during pathological conditions in the mature brain. Employing adult wild type and global Pkn1 knockout (Pkn1-/-) mice, we observed that Pkn1 knockout indeed imparts a protective phenotype in both, in vitro and in vivo stroke models. However, this was not associated with enhanced AK

Stroke is currently the second leading cause of death worldwide, and it accounts for approximately 3-7% of total healthcare expenditures worldwide. Cerebral ischemic stroke has known to cause irreversible damage to the brain by variety mechanisms of excitotoxicity and apoptosis within hours after hypoxic challenge. Recent evidence suggests that a ketogenic diet may reduce infarct volume and neuronal damage in ischemic stroke models. However, the connection between physiological changes induced by the diet with the pathological alterations in hypoxic susceptibility remains unclear. In this rese

Stroke is a preeminent contributor of the global burden of diseases. Hypothermia, among other therapeutic approaches, has been proposed to promote neural survival after stroke, yet the physiological cooling remains ineffective and induces collateral side effects. The thermoregulatory mechanisms are under the control of neuronal identities that connect peripheral signals of the central nervous system, which are predominantly conveyed into the hypothalamus. Here, we aimed to identify a thermoregulatory neuronal subpopulation located at the dorsomedial hypothalamus (DMH) and investigate the DMH-p

…may improve re-myelination and provide neuroprotection in the central nervous system (CNS), following immune-mediated damage described in a mouse model that mimics MS-like disease.Using the myelin oligod

Cytokine receptor-like factor 3 (CRLF3) is an phylogenetically ancient class 1 cytokine receptor present in all major eumetazoan taxa ranging from cnidarians to mammals. In humans, CRLF3 is expressed in various tissues and has been associated with proliferation, differentiation, cell survival and some diseases. Our studies on insect neurons and human iPSC-derived neurons demonstrated that CRLF3 (whose insect-endogenous ligand is still unidentified) can be activated by human erythropoietin (EPO) and its non-erythropoietic splice variant EV-3. Under apoptogenic conditions, CRLF3 initiates pro-su