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Blood-Brain Barrier Permeable Multimodal Imaging Agents for Neurodegenerative Diseases

用于神经退行性疾病的血脑屏障渗透性多模态成像剂

基本信息

批准号：
10740351
负责人：
LIVIU M. MIRICA
金额：
$ 178.37万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10740351
关键词：
Affect Affinity Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease related dementia Amyloid Amyloid Proteins Amyloid beta-Protein Amyloid deposition Amyotrophic Lateral Sclerosis Anti-Inflammatory Agents Antioxidants Autopsy Binding Biology Brain Cause of Death Chelating Agents Chemicals Chemistry Development Diagnosis Diagnostic Disease Early Diagnosis Exhibits Generations Health Human Image Inorganic Chemicals Ions Kinetics Lewy Body Dementia Ligands Magnetic Resonance Imaging Mission Multimodal Imaging Mus Neurodegenerative Disorders Organic Chemicals Oxidation-Reduction Oxidative Stress Parkinson Disease Peptides Persons Play Positron-Emission Tomography Proteins Public Health Reactive Oxygen Species Reporting Research Seat Belts Senile Plaques Series Testing Thermodynamics Transgenic Mice United States United States National Institutes of Health Validation Work abeta oligomer alpha synuclein blood-brain barrier crossing blood-brain barrier permeabilization design diagnostic tool frontotemporal degeneration imaging agent imaging approach imaging system improved in vivo mouse model neuroinflammation neuropathology new therapeutic target novel novel diagnostics optical imaging targeted agent tau-1

项目摘要

Project Summary / Abstract The aggregation of peptides and proteins plays a key role in many devastating neurodegenerative disorders, including Alzheimer's disease (AD) and other AD-related dementias (ADRD) such as Lewy Body dementia (LBD) and Frontotemporal degeneration (FTD), as well as Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Among these amyloid disorders or proteinopathies, Alzheimer's disease (AD) is the most common neurodegenerative disease and the sixth leading cause of death in United States. Around 6 million people are presently diagnosed with AD in the US, and the number is expected to reach 14 million by 2050. To date there is no disease-modifying treatment for AD and its diagnosis with high accuracy requires a detailed post-mortem examination of the brain. While the main neuropathological hallmark of AD is the deposition of amyloid plaques comprising the amyloid beta (Aβ) peptide, new therapeutic targets also include the phosphorylated tau (p-tau) aggregation, as well as reactive oxygen species (ROS) generation, neuroinflammation, and oxidative stress. Therefore, there is a huge unmet need to develop diagnostic agents that can detect at an earlier stage the formation of oligomeric aggregates of the various amyloid proteins involved in proteinopathies (such as Aβ and p-tau in AD, and α-synuclein in PD), as well as target other hallmarks of these disorders such as neuroinflammation and oxidative stress. Herein, we plan to employ a fundamental chemical approach to generate novel blood-brain barrier permeable multifunctional and dual PET/MRI imaging agents and evaluate in vivo their ability as diagnostic agents for AD and ADRD. In these studies, we will employ novel organic and inorganic chemical design principles and synthetic approaches, along with the detailed characterization of the developed bioinorganic systems for imaging/diagnostic applications. Progress in all presented research directions will lead to the development and optimization of novel diagnostic agents for advancing human health.

项目摘要/摘要