Inflammatory Process in Alzheimer's and Parkinson's Diseases: Central Role of Cytokines

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most widespread neurological disorders (NDs) characterized by degeneration of cognitive and motor functions due to malfunction and loss of neurons in the central nervous system (CNS). Numerous evidences have established the role of neuroinflammation in the AD and PD pathology. The inflammatory components such as microglia, astrocytes, complement system and cytokines are linked to neuroinflammation in the CNS. More specifically, cytokines have been found to play a central role in the neuroinflammation of AD and PD. A number of studies have demonstrated abnormally elevated levels of inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF) in AD and PD patients. Activated microglial cells have been shown to be involved in the secretion of pro-inflammatory cytokines such as IL-1, IL-6, TNF-α and transforming growth factor-β, thereby contributing towards the progress of NDs. In addition, studies on AD pathogenesis have demonstrated that microglia produce beta-amyloid protein (Aβ), which by itself is pro-inflammatory and causes activation of several inflammatory components. Similarly, chronic inflammation caused by microglial cells is the fundamental process involved in the destruction of neurons associated with dopamine (DA)-production in the brain of PD patients. Hence, there is a need to explore the key inflammatory components in AD and PD pathogenesis in order to fully understand the root cause and establish a substantial link between these two disorders. Such knowledge will help in better management and treatment of AD and PD.

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

“…Thus, tissue invasion of blood-derived leukocytes of the adaptive immune system (T and B lymphocytes) is prominent in MS and widely accepted to be disease-promoting 31 . In contrast, the pathogeneses of PD and AD are thought to be naturally occurring processes that involve innate components such as microglia, astrocytes, the complement system, and cytokines 32 . The immunomodulatory properties of SP and its role in autoimmune neuroinflammation have been investigated in more detail using the experimental autoimmune encephalomyelitis (EAE) model, as it resembles MS 33,34 .…”

The Role of mPGES-1 in Inflammatory Brain Diseases

“…36) The combined treatment of Aβ [31][32][33][34][35] and PGE 2 induced apoptosis in mPGES-1 deficient neurons to the similar level as Aβ 31-35 -treated wild-type neurons. Furthermore, in an in vivo model of AD, genetic disruption of mPGES-1 in Tg2576 mice has been demonstrated to reduce the accumulation of microglia around SPs and attenuated learning impairments determined by the Morris water maze test.…”

“…Inflammatory reactions, such as glial activations and production of proinflammatory cytokines around SPs have been demonstrated to accompany the neurodegeneration in AD. 31) Although epidemiological studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit COX activity can reduce the risk of developing AD, 32) clinical trials of NSAIDs in AD patients have unfortunately not been very fruitful. The protective effects of NSAIDs have been also shown in a transgenic mouse model of AD demonstrating that NSAIDs reduced amyloid deposition and microglial activation.…”

“…The involvement of mPGES-1 in AD pathology was examined by using primary neurons obtained from mPGES-1 deficient mice, which exhibit an absence of PGE 2 production and less apoptosis after stimulation with Aβ fragment 31-35 (Aβ [31][32][33][34][35] ).…”

Alzheimer’s disease and cytokine IL-10 gene polymorphisms: is there an association?

“…Activated microglia and astrocyte clusters at sites of neuritic plaques release a variety of inflammatory mediators 15 , including pro-and anti-inflammatory cytokines that play critical roles in the development and progression of AD 16,17,18,19 . The associations between AD and inflammatory biomarkers, including the interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-12, IL-18, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and the C-reactive protein have been registered with controversial results 20 .…”