Physiology and Pathology of Neuroimmunology: Role of Inflammation in Parkinson’s Disease

Abstract

Parkinson's disease (PD) is a neurodegenerative disease that affects 1% of the population aged 65 and over and is the second most common neurodegenerative disease next to Alzheimer's disease. Interneuronal proteinaceous inclusions called Lewy bodies (LB) and a selective degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNPC) are the main features of PD pathology. The most common clinical manifestations are rigidity, tremor, bradykinesia, postural instability, sleep disorders, alterations in gait, smell, memory, and dementia. Genetic and environmental factors are involved in PD, and, recently, oxidative stress, proteasome-mediated protein degradation, and inflammation have acquired relevance as major mechanisms of neuronal dysfunction. Increased levels of reactive oxygen and nitrogen species in the brain contribute to greater vulnerability of proteins to nitro-oxidative modification and to greater degrees of aggregation. These protein aggregates contain a variety of proteins of which α-synuclein appears to be the main structural component. Interestingly, α-synuclein can be secreted by neuronal cells and may lead the initiation and the maintenance of inflammatory events through the activation of microglia, which contributes to dopaminergic neuron depletion. New evidence also suggests that PD may be the result of an autoimmune response in which the immune cells recognize the neurons as foreign elements and would act against them, causing their death.

Effect of Vasicinone against Paraquat-Induced MAPK/p53-Mediated Apoptosis via the IGF-1R/PI3K/AKT Pathway in a Parkinson’s Disease-Associated SH-SY5Y Cell Model

“…It is distinguished by the selective degeneration of dopamine-producing neurons in the substantia nigra pars compacta [1], causing striatal dopamine deficiency and intracellular α-synuclein aggregation (Lewy bodies), which are the neuropathological hallmarks of Parkinson’s disease. The resulting dopamine deficiency leads to movement disorders that include rigidity, tremors at rest, slowness, involuntary movement, postural instability and freezing [2]. However, understanding the etiology and pathogenesis of PD remains elusive.…”

Extended perfusion protocol for MS lesion quantification

“…also evidence of persistent BBB abnormalities in chronic inactive lesions [16]. Since the impairment of BBB function is of vital importance for the pathogenesis of MS, many treatment strategies target the resolution of inflammation and protection of BBB function [1,2]. Consequently, the detection and accurate quantification of the BBB permeability are very important for the diagnosis, determination of disease activity and estimation of treatment efficacy in MS.…”

“…Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) usually affecting young adults. Although the etiology of MS is largely unknown, it is considered primarily an autoimmune disease in which activated myelin-specific T-cells migrate from the periphery to the CNS, by crossing the blood-brain barrier (BBB), and induce the formation of new inflammatory demyelinating lesions [1,2]. Recent studies have emphasized the crucial role the BBB dysfunction plays in the inflammatory events that take place in MS [3,4].…”

“…Histopathological and magnetic resonance imaging (MRI) studies reported BBB abnormalities not only in acute active inflammatory MS lesions but also in inactive, non-enhancing lesions and the normal appearing white matter (NAWM) as well [5][6][7]. According to research studies concerning the development of drug therapies in MS, the leukocyte passage across the BBB is very important for disease pathophysiology [8,9] and resolution of inflammation along with the protection of BBB function is the therapeutic target for many proposed MS treatments [1,2].…”

Glycan Shedding in both the Blood and CSF: Initial Predictor of Immune Attack in Autoimmune Encephalomyelitis?

“…Considering the integrity of blood-brain barrier (BBB) prevents the entry of immune cells and antibodies into the CNS [6]. Moreover, diverse neuro-inflammation is the basic pathologic change of NMO, MS and autoimmune GFAP astrocytopathy closely linked to the breakdown of BBB [7], the interplay of neuro-inflammation and BBB dysfunction may seriously result in neurological disturbance [8,9]. To date, the state of BBB in these diseases is not fully demonstrated, and the exploration of this issue may facilitate the understanding of these diseases and offer novel therapies.…”