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Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance Center for Brain Health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

Iron-handling solute carrier SLC22A17 as a blood-brain barrier target after stroke

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Neural Regeneration Research 2025年第11期20卷 3207-3208页

作者： Xueqi Ren Wenlu Li Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Neuroprotection Research Laboratories Departments of Radiology and NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

The pathophysiology of ischemic stroke is complex and multifactorial,involving various forms of cell death such as apoptosis,autophagy,and necrosis.A recent study suggests that oxidative and inflammatory stress can induce ferroptosis,a specialized form of cell death characterized by the accumulation of lipid peroxides dependent on intracellular iron overload(Li and Jia,2023).

关键词： death specialized barrier

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第9期20卷 2556-2570页

作者： Yongting Lv Hongfu Li Department of neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Medical genetics and Center for Rare disease Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Nanhu Brain-Computer Interface Institute HangzhouZhejiang Province

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely *** principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial *** biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even *** these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and *** light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and ***,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal *** fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration *** DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related *** is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease *** the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable *** review summarizes the lat

关键词： amyotrophic lateral sclerosis biomarker blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain prognosis TAR DNA-binding protein 43

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

CMT1A current gene therapy approaches and promising biomarkers

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Neural Regeneration Research 2023年第7期18卷 1434-1440页

作者： Marina Stavrou Kleopas AKleopa Neuroscience Department The Cyprus Institute of Neurology and GeneticsNicosiaCyprus Center for Neuromuscular Disorders The Cyprus Institute of Neurology and GeneticsNicosiaCyprus

Charcot-Marie-Tooth neuropathies(CMT)constitute a group of common but highly heterogeneous,non-syndromic genetic disorders affecting predominantly the peripheral nervous *** type 1A(CMT1A)is the most frequent type and accounts for almost~50%of all diagnosed CMT ***1A results from the duplication of the peripheral myelin protein 22(PMP22)*** of PMP22 protein overloads the protein folding apparatus in Schwann cells and activates the unfolded protein *** leads to Schwann cell apoptosis,dys-and de-myelination and secondary axonal degeneration,ultimately causing neurological *** the last decades,several different gene therapies have been developed to treat *** all of them remain at the pre-clinical stage using CMT1A animal models overexpressing *** therapeutic goal is to achieve gene silencing,directly or indirectly,thereby reversing the CMT1A genetic mechanism allowing the recovery of myelination and prevention of axonal *** promising treatments are rapidly emerging,treatment-responsive and clinically relevant biomarkers are becoming *** biomarkers and sensitive clinical evaluation tools will facilitate the design and successful completion of future clinical trials for CMT1A.

关键词： axonal degeneration biomarkers Charcot-Marie-Tooth disease gene therapy inherited neuropathy mouse models

Novel concept of endoscopic device delivery station system for rapid and tight attachment of polyglycolic acid sheet

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World Journal of Gastroenterology 2018年第2期24卷 211-215页

作者： Hirohito Mori Hideki Kobara Noriko Nishiyama Tsutomu Masaki departments of Gastroenterology and neurology Kagawa University

AIM To evaluate appropriate and rapid polyglycolic acid sheet(PGAs) covering time using device delivery station system(DDSS).METHODS This pilot basic study was conducted to evaluate the potential of accurate and rapid PGAs delivery using DDSS. Three 11-month-old female Beagle dogs were used in this study. Two endoscopic submucosal dissections(ESDs) 4 cm in diameter were performed in lesser curvature of middle gastric body and greater curvature of antrum(total 6 ESDs performed). DDSS(3 cm length, 12 mm in outer diameter) has 2 chambers which 16 cm^2 large 2 PGAs were stored, and DDSS was attached post ESD ulcers, respectively. Beriplast P?(CSL Behring K.K., Tokyo, Japan)(combination of fibringlue and thrombin) was applied equally to the artificial ulcer, and tight attachment of 2 PGAs with DDSS were completed. The evaluation items were covering times, post ESD bleeding and perforation during *** The covering time of PGAs(defined as the duration from the beginning of endoscope insertion into the mouth to the end of the fibrin glue coating process) was 6.07(4.86-8.29) min. There was no postESD bleeding(1-7 d after ESD), and there was no perforation during *** DDSS was very useful for rapid delivering and tight attachment of PGAs, and has potentials of multipurpose delivery station system.

关键词： Post-endoscopic submucosal dissection ulcers Bleeding Polyglycolic acid sheet Rapidly delivery Tightly attachment

Breaking out from the neuroprotective logjam:combined treatment with remote ischemic conditioning and minocycline in the prehospital setting

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Neural Regeneration Research 2015年第4期10卷 537-539页

作者： Jung Mi Park David C.Hess departments of neurology Georgia Regent’s University

The only two treatments effective for acute ischemic stroke are reperfusion therapies. Despite testing of hundreds of neuroprotective agents and treatments, tissue plasminogen activator （tPA）, approved by the Food and Drug Administration （FDA） in 1996, remains the only FDA-approved drug for the treatment of ischemic stroke. Recently,

关键词： Breaking out from the neuroprotective logjam RIC

Management of a large mucosal defect after duodenal endoscopic resection

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World Journal of Gastroenterology 2016年第29期22卷 6595-6609页

作者： Shintaro Fujihara Hirohito Mori Hideki Kobara Noriko Nishiyama Tae Matsunaga Maki Ayaki Tatsuo Yachida Tsutomu Masaki departments of Gastroenterology and neurology Kagawa University Faculty of Medicine

Duodenal endoscopic resection is the most difficult type of endoscopic treatment in the gastrointestinal tract(GI) and is technically challenging because of anatomical specificities. In addition to these technical difficulties, this procedure is associated with a significantly higher rate of complication than endoscopic treatment in other parts of the GI tract. Postoperative delayed perforation and bleeding are hazardous complications, and emergency surgical intervention is sometimes required. Therefore, it is urgently necessary to establish a management protocol for preventing serious complications. For instance, the prophylactic closure of large mucosal defects after endoscopic resection may reduce the risk of hazardous complications. However, the size of mucosal defects after endoscopic submucosal dissection(ESD) is relatively large compared with the size after endoscopic mucosal resection, making it impossible to achieve complete closure using only conventional clips. The over-the-scope clip and polyglycolic acid sheets with fibrin gel make it possible to close large mucosal defects after duodenal ESD. In addition to the combination of laparoscopic surgery and endoscopic resection, endoscopic full-thickness resection holds therapeutic potential for difficult duodenal lesions and may overcome the disadvantages of endoscopic resection in the near future. This review aims to summarize the complications and closure techniques of large mucosal defects and to highlight some directions for management after duodenal endoscopic treatment.

关键词： Endoscopic mucosal resection Endoscopic submucosal dissection Duodenum Complication Bleeding Perforation Over-the-scope clip Clip Closure Endoscopic full-thickness resection

Oval mucosal opening bloc biopsy after incision and widening by ring thread traction for submucosal tumor

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World Journal of Gastroenterology 2017年第39期23卷 7185-7190页

作者： Hirohito Mori Hideki Kobara Yu Guan Yasuhiro Goda Nobuya Kobayashi Noriko Nishiyama Tsutomu Masaki Department of Gastroenterology and neurology Kagawa University departments of Pharmacology Kagawa University

Gastric submucosal tumors(SMTs) less than 2 cm are generally considered benign neoplasms, and endoscopic observation is recommended, but SMTs over 2 cm, 40% of which are gastrointestinal stromal tumors(GISTs), have malignant potential. Although the Japanese Guidelines for GIST recommend partial surgical resection for GIST over 2 cm with malignant potential as well as en bloc large tissue sample to obtain appropriate and large specimens of SMTs, several reports have been published on tissue sampling of SMTs, such as with endoscopic ultrasound sound fine needle aspiration, submucosal tunneling bloc biopsy, and the combination of bite biopsy and endoscopic mucosal resection. Because a simpler, more accurate method is needed for appropriate treatment, we developed oval mucosal opening bloc biopsy after incision and widening by ring thread traction for submucosal tumor(OMOB) approach. OMOB was simple and enabled us to obtain large samples under direct procedure view as well as allowed us to restore to original mucosa.

关键词： Gastric submucosal tumors Gastrointestinal stromal tumor Reversible opening biopsy Endoscopic ultrasonography Large sample