Research in the past decades has unfolded the multifaceted role of Fragile X mental retardation protein (FMRP) and how its absence contributes to the pathophysiology of Fragile X syndrome (FXS). Excess signaling through group 1 metabotropic glutamate receptors is commonly observed in mouse models of FXS, which in part is attributed to dysregulated translation and downstream signaling. Considering the wide spectrum of cellular and physiologic functions that loss of FMRP can affect in general, it may be advantageous to pursue disease mechanism based treatments that directly target translational components or signaling factors that regulate protein synthesis. Various FMRP targets upstream and downstream of the translational machinery are therefore being investigated to further our understanding of the molecular mechanism of RNA and protein synthesis dysregulation in FXS as well as test their potential role as therapeutic interventions to alleviate FXS associated symptoms. In this review, we will broadly discuss recent advancements made towards understanding the role of FMRP in translation regulation, new pre-clinical animal models with FMRP targets located at different levels of the translational and signal transduction pathways for therapeutic intervention as well as future use of stem cells to model FXS associated phenotypes.

The biological mechanisms of autism spectrum disorders (ASDs) are largely unknown in spite of extensive research. ASD is characterized by altered function of multiple brain areas including the temporal cortex and by an increased synaptic excitation:inhibition ratio. While numerous studies searched for evidence of increased excitation in ASD, fewer have investigated the possibility of reduced inhibition. We characterized the cortical γ-amino butyric acid (GABA)ergic system in the rat temporal cortex of an ASD model [offspring of mothers prenatally injected with valproic acid (VPA)], by monitoring inhibitory post-synaptic currents (IPSCs) with patch-clamp. We found that numerous features of inhibition were severely altered in VPA animals compared to controls. Among them were the frequency of miniature IPSCs, the rise time and decay time of electrically-evoked IPSCs, the slope and saturation of their input/output curves, as well as their modulation by adrenergic and muscarinic agonists and by the synaptic GABAA receptor allosteric modulator zolpidem (but not by the extra-synaptic modulator gaboxadol). Our data suggest that both pre- and post-synaptic, but not extra-synaptic, inhibitory transmission is impaired in the offspring of VPA-injected mothers. We speculate that impairment in the GABAergic system critically contributes to an increase in the ratio between synaptic excitation and inhibition, which in genetically predisposed individuals may alter cortical circuits responsible for emotional, communication and social impairments at the core of ASD.

Dengue is a mosquito-borne viral disease (arboviral) caused by the Dengue virus. It is one of the prominent public health problems in tropical and subtropical regions with no effective vaccines. Every year around 400 million people get infected by the Dengue virus, with a mortality rate of about 20% among the patients with severe dengue. The Dengue virus belongs to the Flaviviridae family, and it is an enveloped virus with positive-sense single-stranded RNA as the genetic material. Studies of the infection cycle of this virus revealed potential host targets important for the virus replication cycle. Here in this review article, we will be discussing different stages of the Dengue virus infection cycle inside mammalian host cells and how host proteins are exploited by the virus in the course of infection as well as how the host counteracts the virus by eliciting different antiviral responses.

Highlights d Sense poly(GP) and antisense poly(PR) DPRs are produced in SCA36 d Unlike in c9ALS/FTD, poly(GP) is soluble and does not aggregate in SCA36 d Poly(GA:GP) chimeric DPRs underlie observed poly(GP) aggregation in c9ALS/FTD d Repeat-targeting ASOs robustly reduce poly(GP) DPRs in SCA36

Alpha (α)-herpesviruses (HSV-1 and HSV-2), like other viruses, are obligate intracellular parasites. They hijack the cellular machinery to survive and replicate through evading the defensive responses by the host. The viral genome of herpes simplex viruses (HSVs) contains viral genes, the products of which are destined to exploit the host apparatus for their own existence. Cellular modulations begin from the entry point itself. The two main gateways that the virus has to penetrate are the cell membrane and the nuclear membrane. Changes in the cell membrane are triggered when the glycoproteins of HSV interact with the surface receptors of the host cell, and from here, the components of the cytoskeleton take over. The rearrangement in the cytoskeleton components help the virus to enter as well as transport to the nucleus and back to the cell membrane to spread out to the other cells. The entire carriage process is also mediated by the motor proteins of the kinesin and dynein superfamily and is directed by the viral tegument proteins. Also, the virus captures the cell's most efficient cargo carrying system, the endoplasmic reticulum (ER)-Golgi vesicular transport machinery for egress to the cell membrane. For these reasons, the host cell has its own checkpoints where the normal functions are halted once a danger is sensed. However, a cell may be prepared for the adversities from an invading virus, and it is simply commendable that the virus has the antidote to these cellular strategies as well. The HSV viral proteins are capable of limiting the use of the transcriptional and translational tools for the cell itself, so that its own transcription and translation pathways remain unhindered. HSV prefers to constrain any self-destruction process of the cell-be it autophagy in the lysosome or apoptosis by the mitochondria, so that it can continue to parasitize the cell for its own survival. This review gives a detailed account of the significance of compartmentalization during HSV pathogenesis. It also highlights the undiscovered areas in the HSV cell biology research which demand attention for devising improved therapeutics against the infection.