NfL
Neurofilament Light Chain (Plasma / CSF NfL)
ニューロフィラメント軽鎖（血漿・髄液 NfL バイオマーカー）
1. Biological & Technical Mechanism
Neurofilament light chain (NfL, encoded by NEFL) is a core structural subunit of neurofilaments that maintain the caliber and conduction velocity of large myelinated axons. When neuroaxonal damage occurs due to neurodegeneration, neuroinflammation, or trauma, NfL is released into the interstitial fluid, CSF, and peripheral blood, where it can be quantified at picogram-per-milliliter sensitivity using Single Molecule Array (Simoa) or electrochemiluminescence assays.
ニューロフィラメント軽鎖（NfL：NEFL遺伝子にコードされる）は、有髄神経線維の軸索径の維持と伝導速度の確保を担う主要な細胞骨格タンパク質です。神経変性や脱髄炎症によって軸索損傷が生じると、NfLが脳脊髄液（CSF）および末梢血中へと放出されます。超高感度デジタルELISA（Simoa等）の普及により、少量の採血からpg/mLオーダーで脳内の神経軸索破壊の「現在進行速度」を定量できるようになりました。
2. Open Science & Clinical Trial Significance
While NfL is not disease-specific, it is an indispensable prognostic and pharmacodynamic biomarker: in ALS it predicts survival slope, in Multiple Sclerosis (MS) it reflects subclinical relapse/lesion activity and treatment response, and in FTD/HD it tracks pre-symptomatic conversion.
NfLは疾患特異的ではないものの、「神経変性の進行速度と治療による神経保護効果」を直接反映する客観的サロゲートマーカーとして極めて重要です。ALSにおける予後予測・薬効評価、多発性硬化症（MS）における無症候性病変活動性の検知、FTDやハンチントン病における発症前進行追跡など、ほぼすべてのCNS臨床試験で測定されています。
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.
Highly sensitive fluid biomarker reflecting both cerebral amyloid-beta plaque burden and early tau tangle phosphorylation in Alzheimer's disease.
Gold-standard 48-point clinical rating scale assessing bulbar, fine motor, gross motor, and respiratory function in ALS clinical trials.
Intermediate filament protein of astrocytes released into CSF and blood during reactive astrogliosis; tracks smoldering PIRA progression in MS and amyloid-induced astrocytic reactivity in Alzheimer's.
Irreversible accumulation of neurological disability occurring outside of clinical relapses, driven by diffuse smoldering neuroinflammation, chronic active lesions, and neuroaxonal loss in MS.
Standard 0.0–10.0 ordinal clinical rating scale quantifying neurological disability across 8 functional systems and ambulation capacity in Multiple Sclerosis.
Open Datasets & Research Publications Related to NfL
Multiple Sclerosis and Viruses: « Liaisons Dangereuses ».
Multiple sclerosis (MS) is a complex, multifactorial neurodegenerative disease with an aetiology that is still partially elusive. Several risk factors are associated with MS development including genetic predisposition and various environmental stressors; however, recently, viral infections have gained significant attention as a crucial environmental trigger. Despite the well-established link between Epstein-Barr virus (EBV) and MS susceptibility, a single-pathogen model fails to clearly characterise the molecular cascades driving the disease, suggesting that the transition from infection to autoimmune response involves more than one viral agent. In this review we examine the speculation that the interactions among different neurotropic viruses could serve a collective causative role in MS, which is under-researched in the literature at present. We summarise contradictory evidence on the role of different viral agents, including the Herpesviridae family (Human Cytomegalovirus, EBV, Herpes Simplex Viruses HSV-1 and HSV-2, and Varicella Zoster Virus), Paramyxoviridae family (Measles Virus and Rubella Virus), Influenza virus, SARS-CoV-2, and Human Endogenous Retroviruses (HERVs). Through interplay within shared molecular pathways, immune modulation, and activation of latent infections, these viruses may collectively influence the inflammatory and demyelinating processes that characterise MS. This review evaluates the etiological role of viral interplay in MS through the cumulative and interactive effects of these pathogens. The available epidemiological, immunological, and experimental data converge on the concept that viral co-exposures act synergistically to shape MS susceptibility in genetically predisposed individuals. Characterising these viral interactions presents a new research direction for the identification of novel biomarkers and the development of preventative strategies through the targeted control of viral networks.
Heterotypic Condensate Formation by Prion Proteins and Pro-Inflammatory S100A9
Liquid-liquid phase separation (LLPS) of biomacromolecules has been shown to influence a large variety of biological processes via the formation of membraneless organelles. Aberrant LLPS, however, has been implicated in a number of oncological and neurodegenerative disorders. Proteins related to Alz...
Pharmacological Inhibition of mTORC1 Reduces Neural Death and Damage Volume After MCAO by Modulating Microglial Reactivity
Preclinical evaluation of novel mTORC1 inhibitors in neurodegenerative models demonstrating reduced neuroinflammation.
Eyes on the prize: a neural basis of perceptual choking under pressure
Even professional athletes sometimes fail to perform when it matters most. This phenomenon, known as choking under pressure, has been observed in a variety of motor and cognitive tasks. Can inordinately large rewards influence even sensory processing, and if so, what might be its neural basis? To pr...
Peripheral immunoinflammatory markers and clinical correlations in Parkinson's disease patients carrying LRRK2 G2385R and R1628P variants
Peripheral inflammation in Parkinsons disease (PD) remains poorly characterised among carriers of Asian-prevalent LRRK2 G2385R and R1628P variants. We investigated plasma immunoinflammatory markers (i.e., IL-6, TNF-, CCL2, CX3CL1, CCL5, and VCAM-1) via multiplex immunoassay in 240 participants: PD-G...
Cumulative and Interactive Effects of Heavy Metal Mixtures Across Neurodegenerative Diseases: A Comparative Review of Alzheimer, Parkinson, Amyotrophic Lateral Sclerosis and Multiple Sclerosis.
Heavy metals and metalloids are persistent environmental contaminants that accumulate in the central nervous system and interact with endogenous essential metals, yet most neurotoxicological research continues to treat metals as independent agents rather than as co-occurring mixtures. This review systematically compares the evidence for cumulative and interactive effects of heavy metal mixtures across four major neurodegenerative diseases-Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)-asking which metal combinations have been directly documented for each disease, and whether these patterns are disease-specific or shared. Following a PubMed search (January 2016-June 2026), 93 unique studies were included (AD: 49; PD: 38; ALS: 19; MS: 18; 31 shared across diseases). Combined exposure to lead, cadmium, arsenic, and mercury is linked to amyloid-beta accumulation and dementia risk in AD; manganese-vanadium co-exposure produces more severe dopaminergic damage in PD than either metal alone, with manganese activating the familial PD gene LRRK2; a multi-metal mixture in ALS was associated with a three-fold higher disease risk independent of genetic susceptibility; and MS showed almost no designed mixture studies despite considerable single-metal data, with conflicting findings across cohorts. Three general mechanisms were identified: competition at shared membrane transporters (notably DMT1), sequestration by metal-binding proteins, and direct synergistic or antagonistic interactions, in which essential elements can modulate toxic-metal handling. Mixture-statistics approaches (WQS, BKMR), already established for AD and PD, should be extended to MS to close this evidence gap.
Disclaimer: This encyclopedia entry is intended for academic neuroscience research and data science reference only, and does not constitute medical advice.