A TTC19 mutation associated with progressive movement disorders and peripheral neuropathy: Case report and systematic review.

BACKGROUND: Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia. Multiple genes are associated with complex III defects. Among them, the mutation of TTC19 is a rare subtype. METHODS: We screened a Chinese boy with weakness of limbs and his non-consanguineous parents by whole exome sequencing and targeted sequencing. RESULTS: We report a Chinese boy diagnosed with mitochondrial complex III defect type 2 carrying a homozygous variant (c.719-732del, p.Leu240Serfs*17) of the TTC19 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance. We provide his clinical manifestation. CONCLUSIONS: A new type of TTC19 mutation (c.719-732del, p.Leu240Serfs*17) was found, which enriched the TTC19 gene mutation spectrum and provided new data for elucidating the pathogenesis of CIII-deficient diseases.

Glymphatic System: Emerging Therapeutic Target for Neurological Diseases.

The newly discovered glymphatic system acts as pseudolymphatic vessels subserving brain waste clearance and is functionally dependent on astrocytic aquaporin-4 channels. The glymphatic system primarily functions during sleep as an interchange between cerebrospinal fluid and interstitial fluid, with cerebrospinal fluid flowing into the parenchyma via the perivascular spaces and then exchanging with interstitial fluid. The discovery of meningeal lymphatics helps refine the conceptual framework of glymphatic pathway, as certain waste products collected alongside perivascular spaces ultimately drain into the cervical lymph nodes via meningeal lymphatics, whose function regulates the functioning of the glymphatic system. The glymphatic and meningeal lymphatic systems are critical for the homeostasis of central nervous system, and their malfunctions complicate cerebral dysfunction and diseases. The present review will shed light on the structure, regulation, functions, and interrelationships of the glymphatic system and meningeal lymphatics. We will also expound on their impairments and corresponding targeted intervention in neurodegenerative diseases, traumatic brain injury, stroke, and infectious/autoimmune diseases, offering valuable references for future research.

Long non-coding RNA SNHG1 relieves microglia activation by downregulating miR-329-3p expression in an in vitro model of cerebral infarction.

Following cerebral infarction, activated microglia cells can release a large amount of inflammatory cytokines, thereby exacerbating neuronal damage. It has been demonstrated that the long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) exerts a protective effect against cerebral infarction. However, its specific role in cerebral infarction and underlying mechanism have yet to be fully elucidated. The present study aimed to investigate the effects of the SNHG1 and microRNA (miR)-329-3p in cerebral infarction and to determine the underlying molecular mechanisms. An in vitro oxygen-glucose deprivation (OGD) model was established using the BV-2 microglial cell line. The mRNA expression levels of SNHG1 and miR-329-3p were analyzed using reverse transcription-quantitative PCR and the protein expression levels of cleaved caspase-3 and caspase-3 were detected using western blotting. The binding relationship between SNHG1 and miR-329-3p was predicted using starBase and verified using a dual luciferase reporter assay. The release of TNF-α and nitric oxide, as well as caspase-3 activity, were detected using appropriate commercial kits. Flow cytometry analysis was performed to measure cell apoptosis. The results of the present study revealed that the expression levels of SNHG1 were upregulated in the OGD-induced BV-2 cell model. miR-329-3p was discovered to directly target SNHG1, and its mRNA expression levels were downregulated in the OGD-induced BV-2 cell model. The SNHG1-plasmid downregulated miR-329-3p expression levels, while this effect was reversed by transfection with the miR-329-3p mimic. The overexpression of SNHG1 or knockdown of miR-329-3p inhibited OGD-induced BV-2 cell activation. In conclusion, the results of the present study suggested that SNHG1 may reduce microglial cell activity by regulating the expression of miR-329-3p, indicating its potential protective role in cerebral infarction.

EDNRA Gene rs1878406 Polymorphism is Associated With Susceptibility to Large Artery Atherosclerotic Stroke.

Objective: We performed this study to investigate whether the EDNRA gene rs1878406 C > T polymorphism is associated with risk of large artery atherosclerosis (LAA) stroke in the Chinese Han population. Methods: Genotyping of rs1878406 was performed in 1,112 LAA stroke patients and 1,192 healthy controls. Multivariate logistic regression analyses were applied to assess the effect of the rs1878406 C > T polymorphism on susceptibility to LAA stroke. Results: A significant increase of LAA stroke risk was found in the recessive model (TT vs. CC/TC, OR = 1.74, 95% CI = 1.23-2.48, p = 0.002) and co-dominant model (TC vs. CC, OR = 1.06, 95% CI = 0.89-1.27, TT vs. CC, OR = 1.79, 95% CI = 1.25-2.55, p = 0.006). However, the interaction between age and genotypes of rs1878406 was not statistically significant, and no significant interactive effect was observed between the rs1878406 C > T polymorphism and sex (p > 0.05). Conclusion: The rs1878406 C > T polymorphism is associated with increased risk of LAA stroke in the Chinese Han population.