Therapeutic Potential of Porcine Liver Decomposition Product: New Insights and Perspectives for Microglia-Mediated Neuroinflammation in Neurodegenerative Diseases

Abstract

It is widely accepted that microglia-mediated inflammation contributes to the progression of neurodegenerative diseases; however, the precise mechanisms through which these cells contribute remain to be elucidated. Microglia, as the primary immune effector cells of the brain, play key roles in maintaining central nervous system (CNS) homeostasis. Microglia are located throughout the brain and spinal cord and may account for up to 15% of all cells in the brain. Activated microglia express pro-inflammatory cytokines that act on the surrounding brain and spinal cord. Microglia may also play a detrimental effect on nerve cells when they gain a chronic inflammatory function and promote neuropathologies. A key feature of microglia is its rapid morphological change upon activation, characterized by the retraction of numerous fine processes and the gradual acquisition of amoeba-like shapes. These morphological changes are also accompanied by the expression and secretion of inflammatory molecules, including cytokines, chemokines, and lipid mediators that promote systemic inflammation during neurodegeneration. This may be considered a protective response intended to limit further injury and initiate repair processes. We previously reported that porcine liver decomposition product (PLDP) induces a significant increase in the Hasegawa’s Dementia Scale-Revised (HDS-R) score and the Wechsler Memory Scale (WMS) in a randomized, double-blind, placebo-controlled study in healthy humans. In addition, the oral administration of porcine liver decomposition product enhanced visual memory and delayed recall in healthy adults. We believe that PLDP is a functional food that aids cognitive function. In this review, we provide a critical assessment of recent reports of lysophospholipids derived from PLDP, a rich source of phospholipids. We also highlight some recent findings regarding bidirectional interactions between lysophospholipids and microglia and age-related neurodegenerative diseases such as dementia and Alzheimer’s disease.

Immunomodulation induced by central nervous system‐related peptides as a therapeutic strategy for neurodegenerative disorders

“…15 Anyway, activated microglia play a potentially harmful role in releasing reactive oxygen species (ROS) and pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα). 16 Once activated, microglia can be a potent immune effector that initiates innate and adaptive immune responses and produce several cytokines, chemokines, and growth factors. 16 Nowadays, it is accepted that the well-controlled peripheral inflammatory reaction after an injury is essential for neuroprotection and regeneration.…”

An Inhibitor of NF-κB and an Agonist of AMPK: Network Prediction and Multi-Omics Integration to Derive Signaling Pathways for Acteoside Against Alzheimer’s Disease

“…AMPK is a key protein for the maintenance of cellular homeostasis (Qiu et al, 2020), playing various roles in promoting M2 polarization of microglia (Chu et al, 2019). It modulates metabolic pathways in cells (Szewczuk et al, 2020). We found that ACT promoted the activation of AMPK.…”

“…Microglia are the primary immune cells in the central nervous system, which are closely associated with a cascade of processes such as brain development, maintenance of neural environment, as well as the responses to injury and repair ( Perea et al, 2020 ). Moreover, microglia can be stimulated to an M1 phenotype and increase the expression of pro-inflammatory cytokines when neuroinflammation-related diseases such as AD occurs ( Tsukahara et al, 2020 ). Studies also demonstrate that the polarization to M1 phenotype is often accompanied by metabolic disorders ( Li L. et al, 2020 ), leading to energy metabolism imbalance and mitochondrial dysfunction ( Agrawal and Jha, 2020 ).…”

Epigenetic Modulation of Microglia Function and Phenotypes in Neurodegenerative Diseases

“…In resting conditions, microglia are seemingly ramified in morphology, characterized by active protrusions and dynamic exploration of the circumambient microenvironment. Once activated, aberrant microglia gradually transform into a motile amoeboid form accompanied by the release of variable cellular products, including chemokines, proinflammatory cytokines, and lipid mediators [ 34 , 35 ]. Microglia can promote the expression of anti-inflammatory and neurotrophic factors, scavenging cellular debris and facilitating nerve repair.…”