Involvement of neuroinflammatory mediators in the pathogenesis of neurodegeneration

Abstract

The primary objective of this review is to understand the role of different inflammatory mediators, mechanisms involved in the disease pathogenesis and to identify new therapeutic approaches involved in the treatment of neurodegerative diseases. Neuronflammation is like a two-edged sword because in acute conditions, or at low levels, it deals with the anomaly and is healing in nature. However, in chronic conditions, or at continued high levels it causes massive damage to the viable host tissue. Neuroinflammation accelerates the progression of neurodegeneration in Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). This review aims to study different inflammatory mediators like prostaglandins, cytokines, microglial activation, astrocytic activation, etc and understand the underlying mechanisms (deposition of misfolded proteins, oxidative stress, lipidperoxidation, mitochondrial dysfunctioning) involved in the disease pathogenesis. This range of inflammatory mediators and underlying pathogenic mechanisms provides a variety of potential targets for new anti-inflammatory agents.

Review on various factors responsible for neurodegenerative disorders

“…Hyperoxia causes toxicity, which entails neurotoxicity. Unbalanced redox states may either contain too many reactive oxygen species (ROS) or cause the antioxidant system to malfunction, resulting in oxidative stress [9]. Mitochondria is known as power house of the cell, perform functions of ATP (Adenosine triphosphate) generation, maintains calcium homeostasis, regulating oxidative stress and neuronal survival.…”

“…The activation neuroinflammatory mediators like, microglia and astrocytes and the subsequent release of inflammatory cytokines and prostaglandin responsible for neuroinflammation, which leads to pathogenesis neurodegenerative disorders [9].…”

Utilizing Reduced Labeled Proton Clearance to Identify Preclinical Alzheimer Disease with 3D ASL MRI

“…Inflammatory signaling of microglia triggers its release of C3a (complement) resulting in EC morphologic shift to immunocompetent cells as EC cell surface C3aR (receptors) are upregulated causing retraction of EC walls via activation of cytoskeletal myosin opening tight junctions [1]. They also express vascular cell adherent molecules (VCAM 1) on the EC surface attracting lymphocytes [1][2][3][4][5][6][7]. The inflammatory response within the interstitial space is muted in comparison to incitement by infection [1,3].…”