Naoki Suzuki

Naoki Suzuki
Tohoku University | Tohokudai · Department of Neurology

MD., PhD.

About

166
Publications
52,288
Reads
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7,668
Citations
Citations since 2016
84 Research Items
6409 Citations
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201620172018201920202021202202004006008001,000
201620172018201920202021202202004006008001,000
Additional affiliations
November 2011 - September 2014
Harvard University
Position
  • PostDoc Position
April 2004 - March 2007
National Center of Neurology and Psychiatry
Position
  • PhD Student

Publications

Publications (166)
Article
Myoblast integrity is essential for skeletal muscle regeneration. Many intracellular proteins are degraded by the proteasome and converted to amino acids by aminopeptidases through the protein degradation pathway. Although we previously reported its importance for myoblast integrity, the involved mechanism remains unclear. In this study, we focused...
Article
Introduction: Centronuclear myopathy is a hereditary congenital muscle disease. It is characterized by generalized muscle hypotonia from early childhood, elongated cacial appearance, mandibular undergroth, and dental malposition. In this report, we discuss the clinical course and management of a patient with centronuclearmyopathy, who developed a...
Article
Full-text available
The physiological significance of skeletal muscle as a secretory organ is now well known but we can only speculate as to the existence of as-yet-unidentified myokines, especially those upregulated in response to muscle contractile activity. We first attempted to establish an “insert-chamber based in vitro exercise model” allowing the miniature but...
Article
Useful and plain prognostic markers for amyotrophic lateral sclerosis (ALS) progression are desired to propose a suitable living setting for patients and their caregivers, and to archive appropriate clinical trials. To archive an additional prognostic marker for ALS progression, we evaluated the usefulness of duration from onset to diagnosis (DOD)...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is an intractable disease that causes respiratory failure leading to mortality. The main locus of ALS is motor neurons. The success of antisense oligonucleotide (ASO) therapy in spinal muscular atrophy (SMA), a motor neuron disease, has triggered a paradigm shift in developing ALS therapies. The causative genes o...
Article
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Background Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons selectively. In particular, weakness in respiratory and swallowing muscles occasionally causes aspiration pneumonia and choking, which can be lethal. Surgery to prevent aspiration, which separates the trachea and esophagus, can reduc...
Article
Objectives: To describe cases of patulous Eustachian tube (PET) or patent ET conditions in oculopharyngeal muscular dystrophy (OPMD). Patients: Four cases of PET or patent ET conditions with OPMD. Main outcome measures: Clinical case records, objective ET function tests (tubo-tympano-aerodynamic graphy and sonotubometry), and swallowing functi...
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Full-text available
Contractile activity is a fundamental property of skeletal muscles. We describe the establishment of a “feeder-supported in vitro exercise model” using human-origin primary satellite cells, allowing highly-developed contractile myotubes to readily be generated by applying electrical pulse stimulation (EPS). The use of murine fibroblasts as the feed...
Preprint
Background We previously used an induced pluripotent stem cell–based drug repurposing approach to demonstrate that ropinirole hydrochloride (ropinirole) attenuated amyotrophic lateral sclerosis (ALS)–specific pathological phenotypes. Here, we assessed the safety and efficacy of ropinirole in ALS patients. Methods We conducted a phase 1/2a trial in...
Article
Sporadic inclusion body myositis (sIBM) is a degenerative, intractable, inflammatory myopathy with an immune pathomechanism. We report on a case of a 44-year-old Japanese man who began developing progressive muscle weakness at age 40. Rheumatoid arthritis (RA) symptoms manifested at 43 with strongly positive anti-cyclic citrullinated peptide antibo...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is an adult-onset incurable motor neuron (MN) disease. The reasons for selective MN vulnerability in ALS are unknown. Axonal pathology is among the earliest signs of ALS. We searched for novel modulatory genes in human MN axon shortening affected by TARDBP mutations. In transcriptome analysis of RNA present in th...
Article
Heat shock protein family B member 8, encoded by HSPB8, is an essential component of the chaperone-assisted selective autophagy complex, which maintains muscle function by degrading damaged proteins in the cells. Mutations in HSPB8 have been reported to cause Charcot-Marie-Tooth type 2L, distal hereditary motor neuropathy IIa, and rimmed vacuolar m...
Article
Objective: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis. Methods: Participants (aged 36-85 years) who completed the core study (RESILIENT) were invited to join an extension study. Individuals continued on same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab, or ma...
Article
Full-text available
The ubiquitin‐proteasome system is a major protein degradation pathway in the cell. Proteasomes produce several peptides that are rapidly degraded to free amino acids by intracellular aminopeptidases. Our previous studies reported that proteolysis via proteasomes and aminopeptidases is required for myoblast proliferation and differentiation. Howeve...
Article
Full-text available
Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial di...
Article
Full-text available
A large number of intracellular proteins are degraded by the ubiquitin-proteasome system, one of the major protein degradation pathways. It produces peptides of several different sizes through protein degradation, and these peptides are rapidly degraded into free amino acids by various intracellular aminopeptidases. Previously, we reported that the...
Article
We evaluated the efficacy of rehabilitation therapy with Hybrid Assistive Limb® (HAL; hereafter HAL therapy) in three patients diagnosed with sporadic inclusion body myositis (sIBM) who were hospitalized to undergo HAL therapy. Among them, one patient participated in eight courses and the other two in two courses of HAL therapy between 2017 and 202...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 c...
Article
Full-text available
Skeletal muscle is one of the most abundant and highly plastic tissues. The ubiquitin-proteasome system (UPS) is recognised as a major intracellular protein degradation system, and its function is important for muscle homeostasis and health. Although UPS plays an essential role in protein degradation during muscle atrophy, leading to the loss of mu...
Article
Full-text available
The ubiquitin–proteasome system has the capacity to degrade polyubiquitinated proteins and plays an important role in many cellular processes. However, the role of Rpt3, a crucial proteasomal gene, has not been investigated in adult muscles in vivo. Herein, we generated skeletal-muscle-specific Rpt3 knockout mice, in which genetic inactivation of R...
Article
Fused in sarcoma (FUS) is genetically and clinicopathologically linked to frontotemporal lobar degeneration (FTLD) and amyo-trophic lateral sclerosis (ALS). We have previously reported that intranuclear interactions of FUS and splicing factor, proline-and glutamine-rich (SFPQ) contribute to neuronal homeostasis. Disruption of the FUS-SFPQ interacti...
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Full-text available
C21ORF2 and NEK1 have been identified as amyotrophic lateral sclerosis (ALS)–associated genes. Both genes are also mutated in certain ciliopathies, suggesting that they might contribute to the same signaling pathways. Here we show that FBXO3, the substrate receptor of an SCF ubiquitin ligase complex, binds and ubiquitylates C21ORF2, thereby targeti...
Article
We describe a rare case of inflammatory myopathy with anti‐PM/Scl antibodies myopathologically presenting as polymyositis with mitochondrial pathology (PM‐Mito). A 74‐year‐old Japanese man developed only slowly progressive proximal dominant muscle weakness and atrophy of the four extremities over the past 3 years. His serum creatine kinase level wa...
Article
Full-text available
Mutations in the PNPLA2 gene cause neutral lipid storage disease with myopathy (NLSDM) or triglyceride deposit cardiomyovasculopathy. We report a detailed case study of a 53-year-old man with NLSDM. The PNPLA2 gene was analyzed according to the reported method. We summarized the clinical, laboratory, and genetic information of 56 patients, includin...
Article
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Amyotrophic Lateral Sclerosis is the most common motor neuron degenerative disease in adults, and TARDBP gene mutations have been reported to be involved in the pathogenesis. We present here how we generated the human induced pluripotent stem cell (hiPSC) line KEIOi001-A / SM4-4-5 from the peripheral blood of a 63-year-old male patient presenting t...
Article
Dysferlinopathy is a group of autosomal recessive muscular dystrophies caused by variants in the dysferlin gene (DYSF), with variable proximal and distal muscle involvement. We performed DYSF gene analyses of 200 cases suspected of having dysferlinopathy (cohort 1), and identified diagnostic variants in 129/200 cases, including 19 novel variants. T...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is an intractable adult-onset neurodegenerative disease that leads to the loss of upper and lower motor neurons (MNs). The long axons of MNs become damaged during the early stages of ALS. Genetic and pathological analyses of ALS patients have revealed dysfunction in the MN axon homeostasis. However, the molecular...
Preprint
Full-text available
Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial di...
Article
Full-text available
Mutations in dysferlin are responsible for a group of progressive, recessively inherited muscular dystrophies known as dysferlinopathies. Using recombinant proteins and affinity purification methods combined with LC/MS/MS, we found that AMPKγ1 was bound to a region of dysferlin located between the third and fourth C2 domains. Using ex vivo laser in...
Article
Full-text available
Objective The aim of this study is to describe and clarify the factors affecting the prognosis of Japanese patients with amyotrophic lateral sclerosis (ALS) undergoing tracheostomy invasive ventilation (TIV) therapy. Methods We conducted a prospective longitudinal observational case-control study using a multicentre registry. ALS patients who star...
Article
Full-text available
Background: Sporadic inclusion body myositis (sIBM) is the most prevalent muscle disease in elderly people, affecting the daily activities. sIBM is progressive with unknown cause and without effective treatment. In 2015, sIBM was classified as an intractable disease by the Japanese government, and the treatment cost was partly covered by the gover...
Article
A global, randomized, double-blind placebo-controlled study was conducted to confirm that BYM338 (bimagrumab), an anti-activin type II receptor antibody, improves motor function in patients with sporadic inclusion body myositis after 52 weeks' treatment consisting of intravenous administration every 4 weeks at doses of 10, 3, and 1 mg/kg. In a Japa...
Article
Amyotrophic lateral sclerosis (ALS) is the most rapidly progressive motor neuron disease (MND) in adults, characterized by the selective death of motor neurons in the motor cortex, brainstem, and spinal cord. Riluzole and edaravone are the only approved drugs available in Japan to date. Approximately 10% of ALS cases are familial in rature, defined...
Article
Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder characterized by the death of upper and lower motor neurons. About 10% of all ALS cases are familial, and we have identified SOD1 and FUS mutations as the most common causes in a consecutive series of 111 familial ALS pedigrees in Japan (Nishiyama A, 2017). From studie...
Article
Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease characterized by a progressive decline in motor function. Genetic analyses have identified several genes mutated in ALS patients, and one of them is Cyclin F gene (CCNF), the product of which (Cyclin F) serves as the substrate-binding module of a SKP1-CUL1-F-box protein (SCF...
Article
Background: Inclusion body myositis is an idiopathic inflammatory myopathy and the most common myopathy affecting people older than 50 years. To date, there are no effective drug treatments. We aimed to assess the safety, efficacy, and tolerability of bimagrumab-a fully human monoclonal antibody-in individuals with inclusion body myositis. Method...
Article
Full-text available
Contraction of cultured myotubes with application of electric pulse stimulation (EPS) has been utilized for investigating cellular responses associated with actual contractile activity. However, cultured myotubes derived from human subjects often exhibit relatively poor EPS-evoked contractile activity, resulting in minimal contraction-inducible res...
Article
Full-text available
Background: The characteristic structure of motor neurons (MNs), particularly of the long axons, becomes damaged in the early stages of amyotrophic lateral sclerosis (ALS). However, the molecular pathophysiology of axonal degeneration remains to be fully elucidated. Method: Two sets of isogenic human-induced pluripotent stem cell (hiPSCs)-derive...
Article
We report the neuropathology of a patient with a family history of amyotrophic lateral sclerosis (ALS) and a p.N345K mutation in the transactivation response DNA‐binding protein 43 kDa (TDP‐43) gene (TARDBP). A 62‐year‐old man had bulbar palsy with progressive weakness in the extremities. Neurological examination revealed evident upper motor neuron...
Article
Full-text available
Background Riluzole is the only approved oral drug for amyotrophic lateral sclerosis (ALS). We performed a retrospective study including ALS patients treated with riluzole, focusing on adverse events. Methods Patients diagnosed with ALS according to the revised El Escorial criteria (World Federation of Neurology) in our center and who were adminis...
Article
Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive non-Hodgkin lymphoma that typically develops in the upper aerodigestive tract. We encountered an ENKTL patient who presented with generalized muscle weakness with eyelid swelling, diplopia, and facial edema. A muscle biopsy revealed lymphocytic infiltration without significant atypia; some lymp...
Article
Full-text available
The tropomyosin-receptor kinase fused gene (TFG) has recently been implicated in several distinct hereditary disorders, including the autosomal-recessive form of complicated hereditary spastic paraplegia called SPG57. Previously, three homozygous variants of the TFG gene were reported in five families with SPG57, in which early onset spastic parapl...
Data
Table S2. Microarray Analysis Identified 1,254 Genes that Were Up- or Downregulated with p Values < 0.05 (Satellite Cells from Satellite Cell-Specific Rpt3 Mice versus Satellite Cells from Control Mice), Related to Figure 7
Article
Full-text available
Adult muscle stem cells (satellite cells) are required for adult skeletal muscle regeneration. A proper balance between quiescence, proliferation, and differentiation is essential for the maintenance of the satellite cell pool and their regenerative function. Although the ubiquitin-proteasome is required for most protein degradation in mammalian ce...
Article
Full-text available
Background GNE myopathy (distal myopathy with rimmed vacuoles) is a rare intractable muscle disease caused by the mutations in GNE gene, with no therapeutic agents at present. The mutations in GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) gene result in a deficiency of the biosynthesis of aceneuramic acid. Aceneuramic acid im...
Article
Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative syndrome characterized by the systemic loss of motor neurons with prominent astrocytosis and microgliosis in the spinal cord and brain. Astrocytes play an essential role in maintaining extracellular microenvironments that surround motor neurons, and are activated by vari...
Article
Background Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by systemic loss of motor neurons. Approximately 10% of ALS cases are familial. In a consecutive series of 111 Japanese familial ALS pedigrees, we have recently identified SOD1 and FUS mutations as the most common causes. Objective To reveal p...
Article
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Progressive and systemic loss of motor neurons with gliosis in the central nervous system (CNS) is a neuropathological hallmark of ALS. Chondroitin sulfate proteoglycans (CSPGs) are the major components of the extracellular matrix of the mammalian CNS, and they inhibit axonal...