Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Aβ) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses.

Methods

We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Aβ-mediated neurotoxicities in AD.  Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD.

Results

In response to various stimuli (e.g., infection, trauma, ischemia, air pollution, de

SUBMITTER: Meier-Stephenson FS 

PROVIDER: S-EPMC8985489 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature