Alzheimer disease (AD) is associated with the aggregation of two amyloid proteins: tau and amyloid-β (Aβ). The results of immunotherapies have shown that enhancing the clearance and suppressing the aggregation of these two proteins are effective therapeutic strategies for AD. We have developed photocatalysts that attach oxygen atoms to Aβ and tau aggregates light irradiation. Photo-oxygenation of these amyloid aggregates reduced their neurotoxicity by suppressing their aggregation both and . Furthermore, photo-oxygenation enhanced the clearance of Aβ in the brain and microglial cells. Here, we describe the effects of photo-oxygenation on tau and Aβ aggregation, and the potential of photo-oxygenation as a therapeutic strategy for AD, acting microglial clearance.
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http://dx.doi.org/10.3389/fnagi.2022.945017 | DOI Listing |
FASEB J
December 2023
Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Aggregation of α-synuclein (α-syn) into amyloid is the pathological hallmark of several neurodegenerative disorders, including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. It is widely accepted that α-syn aggregation is associated with neurodegeneration, although the mechanisms are not yet fully understood. Therefore, the inhibition of α-syn aggregation is a potential therapeutic approach against these diseases.
View Article and Find Full Text PDFACS Chem Neurosci
August 2023
Laboratory of Synthetic Organic Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Int J Biol Macromol
June 2023
Department of Chemistry, School of Chemistry and Chemical Engineering, Northwestern Polytechnical University, Xi'an 710072, PR China. Electronic address:
Photoinduced modulation of Aβ aggregation has emerged as a therapeutic option for treating Alzheimer's disease (AD) due to its high spatiotemporal controllability, noninvasive nature, and low systemic toxicity. However, existing photo-oxidants have the poor affinity for Aβ, low depolymerization efficiency, and difficulty in crossing the blood-brain barrier (BBB), hindering their application in the treatment of AD. Here, through hydrophobic interactions and hydrogen bonding, we integrated the near-infrared (NIR) photosensitizer indocyanine green with transferrin (denoted as TF-ICG), a protein with a high affinity for Aβ, and demonstrated its anti-amyloid activity in vitro.
View Article and Find Full Text PDFFront Aging Neurosci
June 2022
Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Alzheimer disease (AD) is associated with the aggregation of two amyloid proteins: tau and amyloid-β (Aβ). The results of immunotherapies have shown that enhancing the clearance and suppressing the aggregation of these two proteins are effective therapeutic strategies for AD. We have developed photocatalysts that attach oxygen atoms to Aβ and tau aggregates light irradiation.
View Article and Find Full Text PDFAdv Exp Med Biol
January 2022
Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Many types of amyloidoses are pathologically characterized by the deposition of amyloid, which is comprised of fibrils formed by abnormally aggregated proteins, in various peripheral tissues and the central nervous system (CNS). Neurodegenerative disorders, such as Alzheimer disease (AD), Parkinson disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), are well-known CNS amyloidoses that are characterized by amyloid deposition both inside and outside of cells. The amyloidogenic proteins of each disease have distinct primary sequences, and they normally function as soluble proteins.
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