C9orf72
Chromosome 9 Open Reading Frame 72 (GGGGCC Hexanucleotide Repeat)
C9orf72遺伝子（GGGGCC 6塩基リピート伸長変異）
1. Biological & Technical Mechanism
Expansion of a GGGGCC (G4C2) hexanucleotide repeat in the first intron of C9orf72 (from <30 repeats in healthy individuals to hundreds or thousands in patients) links ALS and FTD along a single clinicopathological spectrum. Pathogenesis involves three overlapping mechanisms: C9orf72 haploinsufficiency (impaired endolysosomal trafficking in microglia), toxic sense/antisense RNA foci sequestering RNA-binding proteins, and repeat-associated non-AUG (RAN) translation producing toxic dipeptide repeat proteins (DPRs: poly-GA, poly-GP, poly-GR, poly-PA, poly-PR).
第9番染色体上の C9orf72 遺伝子イントロン領域における GGGGCC 6塩基リピート配列の異常伸長（健常者では30回未満、患者では数百〜数千回）は、ALSと前頭側頭型認知症（FTD）が同一の遺伝的・病理的スペクトラム上にあることを決定づけた重要因子です。①C9orf72タンパク質減少によるミクログリアのリソソーム機能不全、②異常伸長RNA凝集体（RNA foci）によるRNA結合タンパク質の機能阻害、③AUG非依存的翻訳（RAN翻訳）による毒性ジペプチドリピートタンパク質（DPR）産生の3つの複合経路で神経変性を誘導します。
2. Open Science & Clinical Trial Significance
Open multi-omics datasets and iPSC-derived motor neuron models carrying C9orf72 expansions are widely used to study nucleocytoplasmic transport defects and microglial neuroinflammation.
C9orf72変異を有するiPS細胞由来運動ニューロンや死後脳snRNA-seqデータセットは、核・細胞質間輸送障害やミクログリアの神経炎症応答を解析するための代表的な公開リソースとして活用されています。
Related Neuroscience Terms & Standards
Nuclear RNA/DNA-binding protein whose cytoplasmic mislocalization, phosphorylation, and loss of nuclear splicing function drive >95% of ALS cases and ~50% of FTD.
Antioxidant enzyme gene; gain-of-toxicity mutations in SOD1 account for ~15-20% of familial ALS and are targeted by the approved antisense oligonucleotide Tofersen.
Axonal cytoskeletal protein released into CSF and blood upon neuroaxonal injury; a cross-disease biomarker of neurodegeneration rate in ALS, MS, AD, and FTD.
Open Datasets & Research Publications Related to C9orf72
Spontaneous slow waves index multiple dimensions of recovery in Disorders of Consciousness
Whether and how residual awareness is expressed in patients with Disorders of Consciousness (DoC) depends on the severity of brain damage and the transient functional state of the cortex at assessment. Classically, DoC are associated with electroencephalographic (EEG) slowing, marked by high-amplitu...
Immediate cortical responses to transcranial magnetic stimulation of the human motor leg area
Background: Immediate transcranial evoked potentials (iTEPs) are ultra-early electroencephalographic responses elicited by single-pulse transcranial magnetic stimulation (TMS) of the primary motor cortical hand area (M1-HAND). Their characteristic latency, waveform, and sensitivity to short-interval...
Not All Entropy Is Equal: Why Representation Matters for Biological Interpretation in Dementia EEG
ObjectiveTo examine what a dementia-associated electroencephalography (EEG) entropy difference permits us to infer about brain dynamics by testing its dependence on permutation-entropy (PE) representation. MethodsFour PE settings represented identical alpha-band data from 1,177 CAUEEG recordings. N...
Assessing respiratory rates and signs of air hunger using the PneumoRator sensor.
ObjectivesTo investigate whether the PneumoRator wearable sensor could accurately assess Respiratory Rate (RR) and signs of air hunger (SAH) compared with clinician-observed assessment in adults with and without breathing pattern disorder (BrPD). DesignA pilot cross-sectional observational study. ...
KCNQ2/3 Regulates Efferent Mediated Slow Excitation of Vestibular Afferents in Mammals
Investigating motor neuron excitability in amyotrophic lateral sclerosis (ALS), this research reveals how KCNQ potassium channel subunits regulate efferent-mediated slow excitation. These electrophysiological findings uncover critical protective mechanisms against motor neuron degeneration.
Evidence-Gated Plasticity and Context-Dependent Consolidation for Multi-Goal Learning in Spiking Neural Networks
Background / Introduction: Biologically inspired spiking neural networks offer a mechanistic framework for adaptive behavior, yet learning multiple goals remains challenging when synaptic updates for different targets interfere. We investigated whether multi-timescale plasticity and context-specific...
Disclaimer: This encyclopedia entry is intended for academic neuroscience research and data science reference only, and does not constitute medical advice.