The impact of chronic neuroinflammation and ageing on cholinergic neurons and glial cells: therapeutic potential of Phytosomal™ curcumin

Abstract

The notion of neuroinflammation such as an inflammatory condition of the central nervous system (CNS) has grown over the last decades. Neuroinflammation refers to the response of the CNS to endogenous or exogenous stimuli that could alter homeostasis. The potential harmful triggers include infections, acute or auto-immune mediated injury as it happens during multiple sclerosis, and accumulation of misfolded or aggregated proteins which are a common mechanism of Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and prion disease. The response of the CNS is mainly mediated by CNS-resident cells such as glial cells like astrocytes and microglia or by CNS-infiltrating cells, such as the macrophages, producing cytokines, chemokines, reactive oxygen species (ROS), and intracellular secondary messengers. For these reasons, neuroinflammation plays a key role in the pathogenesis of neurodegenerative disorders in which glial activation is associated with neuronal loss. In the case of AD, the first neuronal population to degenerate is the cholinergic neurons located in the medial septum (MS) of the basal forebrain (BF) and responsible for cognitive and motor functions. In the past 40 years, several studies suggested that alterations in cholinergic transmission contribute to the establishment and progression of AD, which led to the formulation of the cholinergic hypothesis of AD. In fact, cholinergic neurons show high vulnerability to inflammatory mechanisms, oxidative stress, and changes in their energy metabolism however, the underlying mechanisms leading to their vulnerability are still unclear. We therefore hypothesized that chronic exposure to neuroinflammatory mediators contributes to increased cholinergic vulnerability affecting their neuronal activity. In addition, we also focused on investigating the effect of an anti-inflammatory food supplement, called Phytosomal™ curcumin (PC) (Indena, Italy), in ameliorating the impact of glial-mediated chronic neuroinflammation on the cholinergic system.

Date of Award	2024
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Erika Gyengesi Bilaver (Supervisor), Yossi Buskila (Supervisor) & Gerald Münch (Supervisor)