Abstract
Parkinson’s disease (PD) is the second-most common neurodegenerative disease in the world, affecting up to 10 million people. This disease mainly happens due to the loss of dopaminergic neurons accountable for memory and motor function. Partial glucocerebrosidase enzyme deficiency and the resultant excess accumulation of glycosphingolipids and alpha-synuclein (α-syn) aggregation have been linked to predominant risk factors that lead to neurodegeneration and memory and motor defects in PD, with known and unknown causes. An increasing body of evidence uncovers the role of several other lipids and their association with α-syn aggregation, which activates the innate and adaptive immune system and sparks brain inflammation in PD. Here, we review the emerging role of a number of lipids, i.e., triglyceride (TG), diglycerides (DG), glycerophosphoethanolamines (GPE), polyunsaturated fatty acids (PUFA), sphingolipids, gangliosides, glycerophospholipids (GPL), and cholesterols, and their connection with α-syn aggregation as well as the induction of innate and adaptive immune reactions that trigger neuroinflammation in PD.
Highlights
Parkinson’s Disease (PD) is an age-related neurodegenerative disease that affects~1-2/1000 people [1]
The biological function of the lipid-α-syn-cytokines-reactive oxygen species (ROS) pathway remains elusive; increasing evidence suggests that certain intracellular lipids and their impact on the induction of α-syn abnormalities, excess generation of proinflammatory cytokines, and ROS are responsible for the propagation of brain inflammation in Parkinson’s disease (PD)
Several immune modulators, such as microglial cells and dopaminergic neuron expressions of CD1d, MHC I, and MHC II molecules, as well as increased brain infiltration of T cell subsets, including CD4+ T cells, CD8+ T cells, and NKT cells, and higher production of proinflammatory cytokines, have been observed in mouse models and human patients with PD [320,321,322,323,324]. Such T cells are known for activation of plasma B cells responsible for production of immunoglobulin G (IgG) and
Summary
Parkinson’s Disease (PD) is an age-related neurodegenerative disease that affects. ~1-2/1000 people [1]. The α-syn aggregates have been linked more precisely to the activation of an innate and adaptive immune system that includes microglial cell activation, proinflammatory cytokine generation, and the loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain [73,74]. Α-syn activity in these roles is dependent on the binding and attraction of α-syn to negatively charged lipids such as GPE, TAG, DAG, GPI, cardiolipin (CL), docosahexaenoic acid (DHA), gangliosides, and other acidic phospholipids that influence the conformational changes and catalysis of the formation of abnormal species of α-syn, which lead to the activation of immune inflammation and neurodegeneration in PD [83,84,85,86,87].
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