Inflammation in neurodegenerative diseases – an update

Abstract

SummaryNeurodegeneration, the progressive dysfunction and loss of neurons in the central nervous system (CNS), is the major cause of cognitive and motor dysfunction. While neuronal degeneration is well-known in Alzheimer's and Parkinson's diseases, it is also observed in neurotrophic infections, traumatic brain and spinal cord injury, stroke, neoplastic disorders, prion diseases, multiple sclerosis and amyotrophic lateral sclerosis, as well as neuropsychiatric disorders and genetic disorders. A common link between these diseases is chronic activation of innate immune responses including those mediated by microglia, the resident CNS macrophages. Such activation can trigger neurotoxic pathways leading to progressive degeneration. Yet, microglia are also crucial for controlling inflammatory processes, and repair and regeneration. The adaptive immune response is implicated in neurodegenerative diseases contributing to tissue damage, but also plays important roles in resolving inflammation and mediating neuroprotection and repair. The growing awareness that the immune system is inextricably involved in mediating damage as well as regeneration and repair in neurodegenerative disorders, has prompted novel approaches to modulate the immune system, although it remains whether these approaches can be used in humans. Additional factors in humans include ageing and exposure to environmental factors such as systemic infections that provide additional clues that may be human specific and therefore difficult to translate from animal models. Nevertheless, a better understanding of how immune responses are involved in neuronal damage and regeneration, as reviewed here, will be essential to develop effective therapies to improve quality of life, and mitigate the personal, economic and social impact of these diseases.

Malathion Neurotoxic Effects on Dopaminergic System in Mice: Role of Inflammation

“…Worthy mentioning, microglia is the resident immune cells (macrophages) of the brain which can be triggered and activated in response to proinflammatory trigger or neuronal death. Then, several reactive oxygen species and proinflammatory factors (e.g., tumor necrosis factor α, interleukin-1β) are produced and in turn, contributing to neurotoxicity and degeneration [34,35]. In this context, OPs including malathion may initiate an inflammatory response leading to the activation of microglia as noticed in the current work.…”

Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol

“…Celastrol exhibits anti-inflammatory and anti-oxidant properties (Allison et al 2001;Jung et al 2007;Faust et al 2009;Kim et al 2009;Venkatesha et al 2012;Wong et al 2012;Yang et al 2014;Sharma et al 2015). In addition to inducing Hsp upregulation to prevent misfolding and aggregation of mutant, disease-associated proteins, celastrol also has the potential to reduce inflammatory and oxidative stress that accompanies neurodegeneration and is thought to exacerbate disease progression (Gao and Hong 2008;Amor et al 2010Amor et al , 2014.…”

Cellular defence or viral assist: the dilemma of HDAC6

“…The extensive inflammatory response upon virus infection may contribute to the development of virus-related disease, which is associated with upregulated expression of proinflammatory mediators, including cytokines, chemokines and adhesion molecules [128]. HDAC6 has been implicated in the regulation of proinflammatory gene [129].…”