APOE2 protects against Aβ pathology by improving neuronal mitochondrial function through ERRα signaling.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease and apolipoprotein E (APOE) genotypes (APOE2, APOE3, and APOE4) show different AD susceptibility. Previous studies indicated that individuals carrying the APOE2 allele reduce the risk of developing AD, which may be attributed to the potential neuroprotective role of APOE2. However, the mechanisms underlying the protective effects of APOE2 is still unclear.

Amyloid β oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction.

Background: Although abnormal accumulation of amyloid beta (Aβ) protein is thought to be the main cause of Alzheimer's disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid β induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aβ deposition and vascular injuries.

Natural killer cells in the central nervous system.

Natural killer (NK) cells are essential components of the innate lymphoid cell family that work as both cytotoxic effectors and immune regulators. Accumulating evidence points to interactions between NK cells and the central nervous system (CNS). Here, we review the basic knowledge of NK cell biology and recent advances in their roles in the healthy CNS and pathological conditions, with a focus on normal aging, CNS autoimmune diseases, neurodegenerative diseases, cerebrovascular diseases, and CNS infections.

METTL3-dependent mA methylation facilitates uterine receptivity and female fertility via balancing estrogen and progesterone signaling.

Infertility is a worldwide reproductive health problem and there are still many unknown etiologies of infertility. In recent years, increasing evidence emerged and confirmed that epigenetic regulation played a leading role in reproduction. However, the function of mA modification in infertility remains unknown.

Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.

Tuberculous meningitis (TBM) is the most severe complication of tuberculosis (TB) and is associated with high rates of disability and mortality. Mycobacterium tuberculosis (M. tb), the infectious agent of TB, disseminates from the respiratory epithelium, breaks through the blood-brain barrier, and establishes a primary infection in the meninges.

eEF2 in the prefrontal cortex promotes excitatory synaptic transmission and social novelty behavior.

Regulation of mRNA translation is essential for brain development and function. Translation elongation factor eEF2 acts as a molecular hub orchestrating various synaptic signals to protein synthesis control and participates in hippocampus-dependent cognitive functions. However, whether eEF2 regulates other behaviors in different brain regions has been unknown.

Deficiency of Autism-Related Gene Dock4 Leads to Impaired Spatial Memory and Hippocampal Function in Mice at Late Middle Age.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that lasts lifelong and causes noticeably higher premature mortality. Although the core symptoms and other behavioral deficits of ASD can persist or be deteriorated from early development to old age, how aging affects the behaviors and brain anatomy in ASD is largely unknown. DOCK4 is an ASD risk gene highly expressed in the hippocampus, and Dock4 knockout (KO) mice display ASD-like behaviors in adulthood (4- to 6-month-old).

Securinine Promotes Neuronal Development and Exhibits Antidepressant-like Effects via mTOR Activation.

Impaired differentiation of newborn neurons or abnormalities at the synapses resulted from stress maladaptation could be the key etiology of depression. Recent studies have shown that mTOR, a crucial factor for neuronal differentiation and synapse development, acts as a common factor that mediates the rapid antidepression effects of several new-class antidepressants. In this study, the antidepressant-like activity of securinine, an alkaloid that has central nervous system stimulation ability, was investigated.

Altered postnatal developmental patterns of ultrasonic vocalizations in Dock4 knockout mice.

Ultrasonic vocalization (USV) characterization is useful for evaluating communication in mouse models of autism spectrum disorder (ASD). Here, by categorizing USVs into 12 types using a comprehensive classification method, we obtained the qualitative and quantitative characteristics of USV repertoire emitted by ASD-related Dock4 knockout (KO) mice and their wild-type (WT) littermates during social isolation over early postnatal development. Notably, USVs emitted by WT pups exhibited a developmental switch from a pattern with more multiple-note calls, which have more complex acoustic structure, lower pitch and larger volume, into one with more single-note calls, which have simpler acoustic structure, higher pitch and smaller volume.

Rho GTPase Regulators and Effectors in Autism Spectrum Disorders: Animal Models and Insights for Therapeutics.

The Rho family GTPases are small G proteins that act as molecular switches shuttling between active and inactive forms. Rho GTPases are regulated by two classes of regulatory proteins, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Rho GTPases transduce the upstream signals to downstream effectors, thus regulating diverse cellular processes, such as growth, migration, adhesion, and differentiation.

Two Autism/Dyslexia Linked Variations of Disrupt the Gene Function on Rac1/Rap1 Activation, Neurite Outgrowth, and Synapse Development.

Autism spectrum disorder (ASD) and dyslexia are both neurodevelopmental disorders with high prevalence in children. Both disorders have strong genetic basis, and share similar social communication deficits co-occurring with impairments of reading or language. However, whether these two disorders share common genetic risks remain elusive.

Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function.

Genetic studies of autism spectrum disorder (ASD) have revealed multigene variations that converge on synaptic dysfunction. DOCK4, a gene at 7q31.1 that encodes the Rac1 guanine nucleotide exchange factor Dock4, has been identified as a risk gene for ASD and other neuropsychiatric disorders.

Balanced Rac1 activity controls formation and maintenance of neuromuscular acetylcholine receptor clusters.

Rac1, an important Rho GTPase that regulates the actin cytoskeleton, has long been suggested to participate in acetylcholine receptor (AChR) clustering at the postsynaptic neuromuscular junction. However, how Rac1 is regulated and how it influences AChR clusters have remained unexplored. This study shows that breaking the balance of Rac1 regulation, by either increasing or decreasing its activity, led to impaired formation and maintenance of AChR clusters.