Inflammation and Alzheimer’s Disease: Mechanisms and Therapeutic Implications by Natural Products

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder with no clear causative event making the disease difficult to diagnose and treat. The pathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and widespread neuronal loss. Amyloid-beta has been extensively studied and targeted to develop an effective disease-modifying therapy, but the success rate in clinical practice is minimal. Recently, neuroinflammation has been focused on as the event in AD progression to be targeted for therapies. Various mechanistic pathways including cytokines and chemokines, complement system, oxidative stress, and cyclooxygenase pathways are linked to neuroinflammation in the AD brain. Many cells including microglia, astrocytes, and oligodendrocytes work together to protect the brain from injury. This review is focused to better understand the AD inflammatory and immunoregulatory processes to develop novel anti-inflammatory drugs to slow down the progression of AD.

Microglia-Mediated Inflammation and Neural Stem Cell Differentiation in Alzheimer’s Disease: Possible Therapeutic Role of KV1.3 Channel Blockade

“…Some protein kinases such as mitogen-activated protein kinase (MAPK), cell division cycle 2 kinase (CDC2) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways have been also identified in AD progression ( Rather et al, 2021 ). Activated MAPK and NF-κB increase the production of pro-inflammatory cytokines promoting APP processing, blood-brain barrier (BBB) disintegration and aggravates tau protein phosphorylation.…”

“…Activated MAPK and NF-κB increase the production of pro-inflammatory cytokines promoting APP processing, blood-brain barrier (BBB) disintegration and aggravates tau protein phosphorylation. Moreover, the formation of neurofibrillary tangles due to p38-MAPK activation leads to neuronal degeneration and finally neuronal death ( Jeong et al, 2014 ; Rather et al, 2021 ).…”

Multiple Roles of Paeoniflorin in Alzheimer’s Disease

“…The inflammatory response of the central nervous system (CNS) is considered to be a very complex defense mechanism. Chemokines secreted by CNS cells, such as TNF- α and IL-1 β , which are involved in the mechanism of inflammation, may play a variety of important roles in AD [ 42 – 45 ].…”

“…PF can reduce cognitive dysfunction via regulating SOCS2/IRS-1 signal transduction and blocking tau hyperphosphorylation. Meanwhile, Paeoniflorin can decrease the contents of TNF- α and IL-1 β in the hippocampus to reduce inflammation [ 42 ]. The involvement of the translocator protein 18 kDa (TSPO) is a biomarker of neuroinflammation in vivo [ 46 , 47 ].…”

Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment

“…AD may affect not only the brain, but also causes release of peripheral biomarkers, such as amyloid β (Aβ) and fractions of amyloid precursor protein (APP) in platelets [ 2 ], and an array of inflammatory factors [ 3 ], which may disclose potential pathophysiological mechanisms and provide an opportunity for early diagnosis of the disease. Chronic inflammation in the brain is one of the main mechanisms involved with AD during the neurodegeneration processes commonly observed in AD [ 4 ]. Oxidative stress, blood-brain barrier permeability, and mitochondrial stress in neurons are potential contributors to the harmful effects of the prolonged neuroinflammation during AD progression [ 5 ].…”