Dictyostelium discoideum: A Model System for Neurological Disorders

Abstract

Background: The incidence of neurological disorders is increasing due to population growth and extended life expectancy. Despite advances in the understanding of these disorders, curative strategies for treatment have not yet eventuated. In part, this is due to the complexities of the disorders and a lack of identification of their specific underlying pathologies. Dictyostelium discoideum has provided a useful, simple model to aid in unraveling the complex pathological characteristics of neurological disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal ceroid lipofuscinoses and lissencephaly. In addition, D. discoideum has proven to be an innovative model for pharmaceutical research in the neurological field.

Scope of review: This review describes the contributions of D. discoideum in the field of neurological research. The continued exploration of proteins implicated in neurological disorders in D. discoideum may elucidate their pathological roles and fast-track curative therapeutics.

Keywords: Alzheimer’s Disease; Dictyostelium discoideum; Huntington’s Disease; Parkinson’s Disease; lissencephaly; model organisms; neurological disorders; neuronal ceroid lipofuscinoses.

Figure 1

Model for phenotypic consequences of interactions between DJ-1, AMPK, mitochondrial respiration and oxidative stress. Mitochondrial respiration is inhibited separately by oxidative stress and DJ-1, both in its oxidized (DJ-1_Ox) and reduced (DJ-1_Red) states (indicated by the bifurcated base of the arrow). DJ-1 also activates phagocytosis (broad arrow) and to a slight extent (narrower arrow) pinocytosis, regardless of its oxidation state (indicated by the bifurcated base of the arrows). DJ-1_Ox, but not DJ-1_Red, inhibits and is inhibited by AMPK. Under oxidative stress mitochondrial respiration is inhibited, ATP production is compromised and AMPK is activated, by oxidative stress both directly (not shown) and via the impaired mitochondrial function. At the same time, DJ-1 is oxidized and inhibits AMPK, opposing the effects of impaired respiration and protecting cells from the downstream phenotypic consequences of chronic AMPK hyperactivity. Reproduced from Chen et al. 2021 [46].