mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.

Glutamate receptors, including mGluR5, are involved in learning and memory impairments triggered by aging and neurological diseases. However, each condition involves distinct molecular mechanisms. It is still unclear whether the mGluR5 cell signaling pathways involved in normal brain aging differ from those altered due to neurodegenerative disorders.

High-Throughput Sequencing of BACHD Mice Reveals Upregulation of Neuroprotective miRNAs at the Pre-Symptomatic Stage of Huntington's Disease.

Huntington's disease (HD) is a genetic disorder marked by transcriptional alterations that result in neuronal impairment and death. MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional regulation and fine-tuning of gene expression. Several studies identified altered miRNA expression in HD and other neurodegenerative diseases, however their roles in early stages of HD remain elusive.

7-Deaza-7-fluoro-2'-C-methyladenosine inhibits Zika virus infection and viral-induced neuroinflammation.

Zika virus (ZIKV) has gained a lot of attention in the past few years due to its rapid spread worldwide and its close association to severe neurological outcomes, such as microcephaly and Guillain-Barre syndrome. In this study, the in vitro and in vivo anti-ZIKV activity of 7-deaza-7-fluoro-2'-C-methyl-adenosine (DFMA) was evaluated. In vitro, using primary mouse neuronal cells and human neural stem cells infected by ZIKV, treatment with DFMA resulted in impaired viral replication and protection against virus-induced cell death.

NVP-BEZ235 (Dactolisib) Has Protective Effects in a Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease and the main cause of dementia. Its major symptom is memory loss, which is a result of neuronal cell death, which is accompanied by neuroinflammation. Some studies indicate the overactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway in this disease, being, thus, a potential target for pharmacological treatment.

Alterations of Calcium Channels in a Mouse Model of Huntington's Disease and Neuroprotection by Blockage of Ca1 Channels.

Huntington’s disease (HD) is a neurodegenerative autosomal dominant disorder, characterized by symptoms of involuntary movement of the body, loss of cognitive function, psychiatric disorder, leading inevitably to death. It has been previously described that higher levels of brain expression of Ca1 channels are involved in major neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Our results demonstrate that a bacterial artificial chromosome (BAC)-mediated transgenic mouse model (BACHD mice) at the age of 3 and 12 months exhibits significantly increased Ca1.

Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide.

Zika virus is a mosquito-borne virus that is associated with neurodegenerative diseases, including Guillain-Barré syndrome and congenital Zika syndrome. As Zika virus targets the nervous system, there is an urgent need to develop therapeutic strategies that inhibit Zika virus infection in the brain. Here, we have engineered a brain-penetrating peptide that works against Zika virus and other mosquito-borne viruses.

The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease.

Huntington's Disease (HD) is an autosomal-dominant neurodegenerative disorder, characterized by involuntary body movements, cognitive impairment, and psychiatric disorder. The metabotropic glutamate receptor 5 (mGluR5) plays an important role in HD and we have recently demonstrated that mGluR5-positive allosteric modulators (PAMs) can ameliorate pathology and the phenotypic signs of a mouse model of HD. In this study, we investigated the molecular mechanisms involved in mGluR5 PAMs effect on memory.

Role of Dynein Axonemal Heavy Chain 6 Gene Expression as a Possible Biomarker for Huntington's Disease: a Translational Study.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive deficits, and psychiatric symptoms. The primary genetic cause is an expansion of cytosine adenine guanine (CAG) nucleotides of the huntingtin gene, which codes an important protein involved with neuronal signaling. The severity of HD correlates with the number of CAG repeats and individuals with longer expansions have an earlier onset and more severe symptoms.

Zika Virus Promotes Neuronal Cell Death in a Non-Cell Autonomous Manner by Triggering the Release of Neurotoxic Factors.

Zika virus (ZIKV) has recently caused a worldwide outbreak of infections associated with severe neurological complications, including microcephaly in infants born from infected mothers. ZIKV exhibits high neurotropism and promotes neuroinflammation and neuronal cell death. We have recently demonstrated that -methyl-d-aspartate receptor (NMDAR) blockade by memantine prevents ZIKV-induced neuronal cell death.

-Methyl-d-Aspartate (NMDA) Receptor Blockade Prevents Neuronal Death Induced by Zika Virus Infection.

Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by -methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine.

N-type Ca channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein. In addition to facilitating neurodegeneration, mutant htt is implicated in HD-related alterations of neurotransmission. Previous data showed that htt can modulate N-type voltage-gated Ca channels (Ca2.

Dissecting the Signaling Pathways Involved in the Crosstalk between Metabotropic Glutamate 5 and Cannabinoid Type 1 Receptors.

The metabotropic glutamate 5 receptor and the cannabinoid type 1 receptor are G protein-coupled receptors that are widely expressed in the central nervous system. Metabotropic glutamate 5 receptors, present at the postsynaptic site, are coupled to Gα proteins and display an excitatory response upon activation, whereas the cannabinoid type 1 receptor, mainly present at presynaptic terminals, is coupled to the G protein and triggers an inhibitory response. Recent studies suggest that the glutamatergic and endocannabinoid systems exhibit a functional interaction to modulate several neural processes.