Photo-Oxygenation as a New Therapeutic Strategy for Neurodegenerative Proteinopathies by Enhancing the Clearance of Amyloid Proteins.

Front Aging Neurosci

Laboratory of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

Published: June 2022

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259952PMC
http://dx.doi.org/10.3389/fnagi.2022.945017DOI Listing

Publication Analysis

Top Keywords

photo-oxygenation therapeutic
8
therapeutic strategy
8
enhancing clearance
8
amyloid proteins
8
suppressing aggregation
8
photo-oxygenation
5
strategy neurodegenerative
4
neurodegenerative proteinopathies
4
proteinopathies enhancing
4
clearance
4

Similar Publications

Photo-oxygenation of histidine residue inhibits α-synuclein aggregation.

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 PDF

Quantitative Assays for Catalytic Photo-Oxygenation of Alzheimer Disease-Related Tau Proteins.

ACS Chem Neurosci

August 2023

Laboratory of Synthetic Organic Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.

Article Synopsis
  • The study investigates catalytic photo-oxygenation as a potential therapy for tauopathies like Alzheimer’s disease, focusing on the complex structure of tau proteins.
  • Researchers developed two assay systems to quantitatively analyze the catalytic activity on tau from human patients, emphasizing the oxygenation of histidine residues.
  • Findings indicate a promising catalyst for oxygenating human tau but reveal differences between heparin-induced aggregated tau and tau from actual Alzheimer’s patients, which may impact the effectiveness of photo-oxygenation strategies.
View Article and Find Full Text PDF

Photooxidative inhibition and decomposition of β-amyloid in Alzheimer's by nano-assemblies of transferrin and indocyanine green.

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 PDF

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 PDF

Photo-Oxygenation: An Innovative New Therapeutic Approach Against Amyloidoses.

Adv 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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!