Astrocytic Ornithine Decarboxylase 1 in Alzheimer's Disease

Abstract

Recent research has shed light on the metabolic changes in reactive astrocytes associated with Alzheimer's disease, contributing to disease pathology. In this article, we summarize key findings related to reactive astrogliosis and how the discovery of the role of the enzyme ornithine decarboxylase 1 can set us on the path to finding more effective therapeutic strategies against neurodegenerative diseases.

Keywords: Alzheimer’s disease; Astrocyte; Urea cycle.

Fig. 1

Astrocytic urea metabolism in normal (left) and AD condition (right). Healthy astrocytes follow non-cyclic urea metabolism (with low expression of enzymes OTC and ODC1), while reactive astrocytes switch to the urea cycle, as seen by the expression of enzymes ODC1 and OTC. The schematic on the right shows the dichotomy of beneficial amyloid clearance and detrimental GABA and H₂O₂ production in reactive astrocytes by the urea cycle, with ODC1 as the bridge. Aβ, Amyloid beta; ODC1, Ornithine Decarboxylase 1; OTC, Ornithine Transcarbamylase; NH₃, Ammonia; GABA, γ aminobutyric acid; H₂O₂, hydrogen peroxide. Adapted from Ju et al. [1]. Created on biorender.com.