Delving into the Latest Updates on Tokyo Metropolitan Institute of Medical Science with Synapse

Restoration of brain function via artificial neural connection - Restoration of locomotor function via artificial neural connection in individuals with spinal cord injury

开始日期2017-04-01

申办/合作机构

Tokyo Metropolitan Institute of Medical Science

JPRN-UMIN000021966

/ CompletedN/A

Project for Promotion of Community Care Program for People Living With Dementia - Development of Japanese version of BPSD Program of Care

开始日期2016-09-01

申办/合作机构

Tokyo Metropolitan Institute of Medical Science

JPRN-UMIN000023742

/ Unknown statusN/AIIT

Study of factors of virus and host sassociated with severe Enterovirus diseases - Study of severe Enterovirus diseases

开始日期2016-07-01

申办/合作机构

Tokyo Metropolitan Institute of Medical Science

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3,007

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2025-03-01·Neural Regeneration Research

Monogenic gene therapy for glaucoma and optic nerve injury

Article

作者: Harada, Chikako ; Harada, Takayuki ; Guo, Xiaoli

The prevalence of glaucoma, the second leading cause of global blindness, is increasing due to aging populations.In glaucoma, degeneration of the optic nerve and retinal ganglion cells (RGCs) causes visual field defects and eventual blindness.Elevated intraocular pressure (IOP) stands out as the best-known factor affecting glaucoma.However, there exists a subtype of glaucoma, known as normal tension glaucoma, that is not associated with high IOP.A recent study has identified various factors involved in glaucoma pathogenesis, including altered retinal blood flow, glutamate neurotoxicity, oxidative stress, and others (Shinozaki et al., 2024).Furthermore, glaucoma patients may exhibit reduced amounts of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) or ciliary neurotrophic factor compared with age-matched controls.Studies indicate that intraocular injections of BDNF can rescue RGCs in a mouse model of optic nerve crush (ONC) through activation of its high-affinity receptor Tropomyosin receptor kinase B (TrkB).However, the transient nature of ligand-dependent activation poses limitations on the efficacy of this treatment.We have developed several systems, described in the following sections, to address and overcome these limitations.However, the transient nature of ligand-dependent activation poses limitations on the efficacy of this treatment.We have developed several systems, described in the following sections, to address and overcome these limitations.Many novel and promising therapies have been reported to stimulate neuroprotection and axon regeneration for glaucoma and optic nerve injury although we mainly introduced our new method of gene therapy using F-iTrkB in this perspective.

2025-02-01·Brain and Development

Chaperone therapy: Stabilization and enhancement of endogenous and exogenous lysosomal enzymes

作者: Suzuki, Yoshiyuki

Chaperone therapy is a new concept of mol. therapeutic approach to protein misfolding diseases, particularly to lysosomal diseases.Initially we started mol. anal. of culture cells, model animals and patients with Fabry disease and G_M1-gangliosidosis.Some mutant enzyme proteins did not express the catalytic activity because of unstable mol. structure in somatic cells.The small mol. compound (chaperone) corrected misfolding of the unstable mutant protein, resulting in restoration of the enzyme activity (chaperone therapy).This pathol. mol. event was studied first in endogenous mutant enzymes.Then a similar mol. interaction was found between the chaperone and the exogenous protein supplied for enzyme replacement therapy (ERT) in Pompe disease.This new chaperone-ERT combination therapy will become another useful technol. in order to expand the application of chaperone therapy to a wide range of lysosomal diseases.Thus, chaperone therapy is expected in future for stabilization and enhancement of exogenously supplied ERT enzymes as well as endogenous mutant enzymes.

2025-01-10·Science

Superstable lipid vacuoles endow cartilage with its shape and biomechanics

Article

作者: James, David E. ; Astrowski, Aliaksandr A. ; van Breukelen, Frank ; Schoeniger, Sandra ; Vadivel, Chella K. ; Plikus, Maksim V. ; Yang, Chao-Chun ; Nguyen, Anh M. ; Chu, Yi-Lin ; Behringer, Richard R. ; Loughry, William J. ; Potma, Eric O. ; Nie, Qing ; Digman, Michelle ; Ingleby, Sandy ; Liu, Yuchen ; Guerrero-Juarez, Christian Fernando ; Schilling, Thomas F. ; Pai, Yun-Ling ; Kohara, Michinori ; Bielajew, Benjamin J. ; Yamaga, Kosuke ; Hsi, Tsai-Ching ; Tran, Bryant Q. ; Bradley, Jeffrey E. ; Datta, Rupsa ; Wang, Xiaojie ; Lin, Sung-Jan ; Weldy, Scott H. ; Kiebish, Michael A. ; Almet, Axel A. ; Hu, Jerry C. ; Prasad, Maneeshi S. ; Athanasiou, Kyriacos A. ; Lim, Norman T.-L. ; Cooper, Kimberly L. ; Liu, Ruiqi ; García-Castro, Martín I. ; Ramos, Raul ; Leiser-Miller, Leith B. ; Peng, Tao ; Santana, Sharlene E. ; Prince, Richard C. ; Cosper, Raymond ; Rasweiler, John J. ; Burns, John T. ; McKechnie, Andrew E. ; Nordberg, Rachel C. ; Hoehn, Kyle L. ; Oh, Ji Won ; Merrill, Amy E. ; Astrowskaja, Aksana ; Pham, Kim T.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis. Consequently, lipochondrocytes grew uniform lipid droplets that resisted systemic lipid surges and did not enlarge upon obesity. Lipochondrocytes also lacked lipid mobilization factors, which enabled exceptional vacuole stability and protected cartilage from shrinking upon starvation. Lipid droplets modulated lipocartilage biomechanics by decreasing the tissue’s stiffness, strength, and resilience. Lipochondrocytes were found in multiple mammals, including humans, but not in nonmammalian tetrapods. Thus, analogous to bubble wrap, superstable lipid vacuoles confer skeletal tissue with cartilage-like properties without “packing foam–like” extracellular matrix.

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