Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?

Abstract

Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these diseases commonly feature chronic neuroinflammation as a hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction and protein aggregation can mutually contribute to the activation of neuroinflammatory response and thus to the onset and progression of these disorders. In the present review, we discuss the contribution of mitochondria dysfunction and neuroinflammation to the aetiology and progression of NDs, highlighting the possibility that new potential therapeutic targets can be identified to tackle neurodegenerative processes and alleviate the progression of these pathologies.

Ultrastructural Changes of Neuroendocrine Pheochromocytoma Cell Line PC-12 Exposed In Vitro to Rotenone

“…A severe limitation of this PC12 cell line model is that in our analysis, we completely missed the interactions among different cells present in the microenvironment of the PD target neurons (substantia nigra). Recently, the role of microglial activation and damage, the activation of the inflammasome, and the different types of cell death occurring in target neurons is emerging from experiments in animals where damaging tissue signals and pathways may be explored [44] (Figure 3). Another limitation of this paper is that several of our data (presence of cellular junction, multivesicular bodies, and synaptic vesicle content) were qualitatively described and not quantitatively evaluated.…”