Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10
Published: Oct. 12, 2022
EDITORIAL article Front. Cell Dev. Biol., 12 October 2022Sec. Death and Survival Volume 10 - 2022 | https://doi.org/10.3389/fcell.2022.1036587
Language: Английский
Movement Disorders, Journal Year: 2024, Volume and Issue: 39(11), P. 2117 - 2119
Published: Aug. 12, 2024
We read with great interest the article by Bademosi and colleagues,1 where they investigated role of SH3GL2 p.G276V on neuron dysfunction in Parkinson's disease (PD). The gene encodes endophilin-A1 (EndoA1) protein, crucial for synaptic vesicle endocytosis blood–brain barrier permeability regulation.1 Two independent signals have been identified to potentially increase PD risk latest European genome-wide association studies (GWAS) meta-analysis: rs13294100 rs10756907.2 Exome sequencing a German cohort suggested variant as an factor. et al1 recently demonstrated that impairs Ca2+ influx-induced autophagy without destabilizing EndoA1. authors found human protein was stable but showed significant decrease number autophagosomes compared control neurons. To clarify between PD, we leveraged whole-genome (WGS) data from Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD; https://amp-pd.org/) release 3.0, consisting 3,105 cases 3,670 controls descent, large-scale genotyping imputed Global Genetics Program (GP2; https://gp2.org/) 5.0, 12,728 10,533 10 different ancestries. Quality analyses are described elsewhere (https://github.com/vitale199/GenoTools/). Variants were annotated using ANNOVAR, Fisher's exact test applied PLINK 1.9. Summary statistics GWAS meta-analyses assessed.2-5 omicSynth resource looking at quantitative trait loci (QTL). Gene-based burden performed RVTESTS. 14,590 variants AMP-PD (Supplementary Table S1). Likewise, 30,719 GP2 Europeans both (one case, two controls) (three cases, one control); however, no (AMP-PD: P = 0.394, odds ratio [OR] 1.296; GP2: 0.869, OR 1.034) (Table 1). This also three African American (AAC) Ashkenazi Jew (AJ) patient. No linkage disequilibrium (LD) observed lead single nucleotide polymorphisms (SNPs). Conditional these most likely signals. common genetic variation Latino nor Asian populations.4, 5 analysis multi-ancestry population3 intronic rs910316833 SNP Fig. QTL revealed six potential functional impacts (top SNPs: rs2145659, rs3758217, rs10756899, rs2383044). Finally, cumulative effect multiple within after conducting rare meta-analyses. Using largest case–control cohorts publicly available date field, Europeans; this not associated consequently does causally explain locus. M.T.P. S.B.C. conceived designed study. A.L.F., A.J.H.M., D.B.R.P., A.N.C. M.B.M. results. A.J.H.M. D.B.R.P. wrote manuscript support A.N.C., M.B.M., All contributed editing final manuscript. work carried out guidance "GP2 Trainee Network" is part funded Aligning Science Across (ASAP) initiative. Data used preparation obtained (GP2). For complete list members, see https://gp2.org. Partnership® (AMP®) (AMP® PD) Knowledge Platform. up-to-date information study, visit https://www.amp-pd.org. ACCELERATING MEDICINES PARTNERSHIP AMP registered service marks United States Department Health Human Services. hosted collaboration via application website (https://amp-pd.org/register-for-amp-pd; https://doi.org/10.5281/zenodo.7904832). Genotyping imputation, quality control, ancestry prediction, processing GenoTools v1.0, GitHub (https://github.com/GP2code/GenoTools). scripts (https://github.com/GP2-TNC-WG/GP2_TRAINEES-SH3GL2/; Zenodo DOI: https://doi.org/10.5281/zenodo.10257319). S1. Supporting Information. Please note: publisher responsible content or functionality any supporting supplied authors. Any queries (other than missing content) should be directed corresponding author article.
Language: Английский
Citations
0
Medicine, Journal Year: 2024, Volume and Issue: 103(34), P. e39405 - e39405
Published: Aug. 23, 2024
Neurodegenerative diseases are complex disorders that significantly challenge human health, with their incidence increasing age. A key pathological feature of these is the accumulation misfolded proteins. The underlying mechanisms involve an imbalance in calcium homeostasis and disturbances autophagy, indicating a likely correlation between them. As most important second messenger, Ca 2+ plays vital role regulating various cell activities, including autophagy. Different organelles within cells serve as storage chambers regulate levels under different conditions. compartments can affect autophagy via channels or other related signaling Researchers propose regulates through distinct signal transduction mechanisms, normal stressful conditions, thereby contributing to occurrence development neurodegenerative diseases. This review provides systematic examination regulatory membranes organelles, well its downstream pathways influence implications for comprehensive analysis may facilitate new drugs provide more precise treatments
Language: Английский
Citations
0
Published: Nov. 12, 2024
The assembly and operation of neural circuits in the brain rely on coordination balance excitatory inhibitory activities. Inhibitory synapses are key regulators functional circuits. However, due to diversity presynaptic neurons, complex composition postsynaptic receptor subunits lack typical dense structure, there relatively few studies regulatory mechanisms for synaptic structure function, insufficient understanding cellular molecular abnormalities neurological neuropsychiatric disorders. Here, we report a crucial role endophilin A1 synapses. We show that directly interacts with scaffold protein gephyrin promotes organization density recruitment/stabilization γ-aminobutyric acid type A receptors via its plasma membrane association actin polymerization promoting Loss by gene knockout mouse hippocampal CA1 pyramidal cells weakens transmission causes imbalance excitatory/inhibitory function circuits, leading increased susceptibility epilepsy. Our findings identify as an iPSD component provide new insights into stabilization postsynapses maintain E/I well pathogenesis
Language: Английский
Citations
0
Published: Nov. 12, 2024
The assembly and operation of neural circuits in the brain rely on coordination balance excitatory inhibitory activities. Inhibitory synapses are key regulators functional circuits. However, due to diversity presynaptic neurons, complex composition postsynaptic receptor subunits lack typical dense structure, there relatively few studies regulatory mechanisms for synaptic structure function, insufficient understanding cellular molecular abnormalities neurological neuropsychiatric disorders. Here, we report a crucial role endophilin A1 synapses. We show that directly interacts with scaffold protein gephyrin promotes organization density recruitment/stabilization γ-aminobutyric acid type A receptors via its plasma membrane association actin polymerization promoting Loss by gene knockout mouse hippocampal CA1 pyramidal cells weakens transmission causes imbalance excitatory/inhibitory function circuits, leading increased susceptibility epilepsy. Our findings identify as an iPSD component provide new insights into stabilization postsynapses maintain E/I well pathogenesis
Language: Английский
Citations
0
Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10
Published: Oct. 12, 2022
EDITORIAL article Front. Cell Dev. Biol., 12 October 2022Sec. Death and Survival Volume 10 - 2022 | https://doi.org/10.3389/fcell.2022.1036587
Language: Английский
Citations
2