TDP-43
TAR DNA-Binding Protein 43 (TARDBP)
TDP-43（TAR DNA結合タンパク質43 / TARDBP遺伝子）
1. Biological & Technical Mechanism
TDP-43 (encoded by the TARDBP gene) is a conserved heterogeneous nuclear ribonucleoprotein (hnRNP) that regulates transcription, pre-mRNA splicing, mRNA transport, and repression of non-conserved 'cryptic exons'. In ~97% of amyotrophic lateral sclerosis (ALS) cases, ~50% of frontotemporal lobar degeneration (FTLD-TDP), and limbic-predominant age-related TDP-43 encephalopathy (LATE), TDP-43 is depleted from the nucleus and forms hyperphosphorylated, ubiquitinated cytoplasmic inclusions.
TDP-43（TARDBP遺伝子によりコードされる）は、通常は神経細胞の核内に局在し、pre-mRNAのスプライシング制御、mRNAの安定化・軸索輸送、および異常な「クリプティックエクソン（隠れたエクソン）」の挿入抑制を担うRNA/DNA結合タンパク質です。筋萎縮性側索硬化症（ALS）の約97%、前頭側頭葉変性症（FTLD-TDP）の約50%において、TDP-43が核から消失して細胞質内に異常リン酸化・ユビキチン化凝集体を形成します。
2. Open Science & Clinical Trial Significance
Loss of nuclear TDP-43 causes cryptic exon inclusion in critical neuronal genes such as STMN2 (Stathmin-2) and UNC13A. Detecting cryptic peptides in CSF and designing antisense oligonucleotides (ASOs) to restore STMN2/UNC13A splicing are major focus areas in ENCALS and bioRxiv neuroscience preprints.
核内TDP-43の機能喪失により、運動ニューロンの軸索再生に必須の STMN2 やシナプス機能に関わる UNC13A にクリプティックエクソンが誤挿入されるメカニズムが解明され、これを標的としたアンチセンス核酸（ASO）創薬や新規バイオマーカー開発がALS研究の最前線となっています。
Related Neuroscience Terms & Standards
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.
Hexanucleotide repeat expansion (GGGGCC) in C9orf72 is the most common genetic cause of both familial ALS and familial frontotemporal dementia (FTD).
Axonal cytoskeletal protein released into CSF and blood upon neuroaxonal injury; a cross-disease biomarker of neurodegeneration rate in ALS, MS, AD, and FTD.
Gold-standard 48-point clinical rating scale assessing bulbar, fine motor, gross motor, and respiratory function in ALS clinical trials.
Open Datasets & Research Publications Related to TDP-43
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.
VCP is a critical component for TDP-43 disaggregase activity in skeletal muscle
TDP-43 aggregates are a unifying pathological feature between several neurodegenerative diseases and myopathies. Mutations in the AAA ATPase protein VCP have been linked to TDP-43 proteinopathies in both brain and skeletal muscle including frontotemporal dementia (FTD), amyotrophic lateral sclerosis...
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. ...
Disclaimer: This encyclopedia entry is intended for academic neuroscience research and data science reference only, and does not constitute medical advice.