Neuroscience
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The intercellular communication within the central nervous system (CNS) is of great importance for in maintaining brain function, homeostasis, and CNS regulation. When the equilibrium of CNS is disrupted or injured, microglia are immediately activated and respond to CNS injury. Microglia-derived exosomes are capable of participating in intercellular communication within the CNS by transporting various bioactive substances, including nucleic acids, proteins, lipids, amino acids, and metabolites. ⋯ Meanwhile, we summarized the molecular mechanisms by which the relevant exosomes exert regulatory effects. Exosomes, derived from microglia stimulated by different environments, regulate other nerve cells during the repair of CNS injury, having beneficial or detrimental effects on CNS repair. A comprehensive understanding of the molecular mechanisms underlying their role can provide a robust foundation for the clinical treatment of CNS injury.
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Autism spectrum disorder (ASD) is a highly prevalent multifactorial disorder characterized by social deficits and stereotypies. Despite extensive research efforts, the etiology of ASD remains poorly understood. However, studies using preclinical models have identified the mechanistic target of rapamycin kinase (mTOR) signaling pathway as a key player in ASD-related features. ⋯ The review also discusses the therapeutic potential of mTOR pathway inhibitors, such as rapamycin, in mitigating ASD characteristics. These insights underscore the importance of the mTOR pathway as a target for future research and therapeutic intervention in ASD. This review innovates by bringing the convergence of disrupted mTOR signaling in preclinical models and clinical data associated with ASD.
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Review Meta Analysis
Unveiling the veil of adipokines: A meta-analysis and systematic review in amyotrophic lateral sclerosis.
Adipokines are proposed to be associated with ALS progression through assorted pathways. Therefore, The present meta-analysis explored the link between various adipokines and ALS progression. ⋯ Our findings revealed that serum concentrations of ghrelin and leptin were higher in ALS patients compared to control, unlike adiponectin.
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Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. ⋯ Knockdown of BRD7 inhibited p53 mitochondrial translocation, leading to reduced apoptosis. Our results suggest that BRD7 plays an important role in the survival of ALS motor neurons. BRD7 knockdown can reduce cellular senescence and apoptosis by inhibiting p21 and p53 mitochondrial translocation.
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Targeted intracranial delivery of molecularly-specific therapies within intricate brain structures poses a formidable challenge due to the heterogeneity of neuronal phenotypes and functions. Here we report the use of an implantable, miniaturized neural drug delivery system permitting dynamic adjustment of pharmacotherapies. ⋯ Remarkably, we demonstrate that micro infusions of U-50488 into the dorsal NASh induces reward-like conditioned place preferences, whereas a mere 1 mm shift ventrally results in conditioned place aversions. The striking precision afforded by this method may prove useful in other neurotherapeutic interventions.