Lipidomics of Bioactive Lipids in Alzheimer’s and Parkinson’s Diseases: Where Are We?

Abstract

Lipids are not only constituents of cellular membranes, but they are also key signaling mediators, thus acting as “bioactive lipids”. Among the prominent roles exerted by bioactive lipids are immune regulation, inflammation, and maintenance of homeostasis. Accumulated evidence indicates the existence of a bidirectional relationship between the immune and nervous systems, and lipids can interact particularly with the aggregation and propagation of many pathogenic proteins that are well-renowned hallmarks of several neurodegenerative disorders, including Alzheimer’s (AD) and Parkinson’s (PD) diseases. In this review, we summarize the current knowledge about the presence and quantification of the main classes of endogenous bioactive lipids, namely glycerophospholipids/sphingolipids, classical eicosanoids, pro-resolving lipid mediators, and endocannabinoids, in AD and PD patients, as well as their most-used animal models, by means of lipidomic analyses, advocating for these lipid mediators as powerful biomarkers of pathology, diagnosis, and progression, as well as predictors of response or activity to different current therapies for these neurodegenerative diseases.

Resolvin D1: A key endogenous inhibitor of neuroinflammation

“…In accordance, higher plasma levels of pro‐inflammatory mediators such as IL‐1β, IL‐2, IL‐8, IL‐6, IL‐17, TNF‐α, iNOS, COX‐1, and COX‐2 have been shown to augment the dopaminergic neurons injuries in PD 59–62 . A review of recent findings shows that several SPMs have beneficial effects on PD, and have a key role in the pathogenesis of PD 12 . Krashia et al showed that patients with PD had higher levels of TNF‐α, interferon‐γ (IFN‐γ), IL‐4, and IL‐10 in the plasma and CSF with significantly lower RvD1 levels than their control subjects 63 .…”

“…They mostly induce significant anti‐inflammatory responses that favor the prevention of AD. For a review of recent findings, see Chiurchiù et al 12 It should be noted that Aβ is an activator of ALX/FPR2 that promotes chemotaxis and oxidative stress and activates microglia 42 . During neuroinflammation, Aβ and pro‐inflammatory chemokines efflux across the BBB and promote the recruitment of leukocytes into the CNS to modulate neuroinflammation and neurodegeneration 43 .…”

“…[59][60][61][62] A review of recent findings shows that several SPMs have beneficial effects on PD, and have a key role in the pathogenesis of PD. 12 Krashia et al showed that patients with PD had higher levels of TNF-α, interferon-γ (IFN-γ), IL-4, and IL-10 in the plasma and CSF with significantly lower RvD1 levels than their control subjects. 63 They indicated that the rats overexpressing human α-synuclein (Syn rats) exhibited altered DA neuron properties and lower striatal dopamine outflow and motor deficits before nigral degeneration.…”

“…8,9 Many beneficial effects of fish oil supplements are associated with the production of these metabolites. On the other hand, changes in the plasma SPMs levels have been described in several neurological diseases including ischemic stroke, 10 depression, 11 Alzheimer's and Parkinson's diseases (AD and PD), 12 amyotrophic lateral sclerosis (ALS), 13 and multiple sclerosis. 14,15 Resolvins have been reported with significant immunoresolvent potentials.…”

Lipidomics and proteomics: An integrative approach for early diagnosis of dementia and Alzheimer’s disease

“…Additionally, the lipid content of membrane lipid rafts is directly linked to amyloidogenesis, a significant pathogenetic component for AD (Ehehalt et al, 2003), which have a higher concentration of saturated fatty acids (FAs) than Frontiers in Genetics frontiersin.org polyunsaturated fats (PUFAs) and sphingolipids, which operate as platforms for Aβ associations with tau and ApoE to facilitate the formation of A oligomers and hyperphosphorylation (Di Paolo and Kim 2011;Huynh et al, 2017). In addition, cortical and free unsaturated FAs induce the assembly of amyloid and tau filaments in vitro (Chiurchiù et al, 2022).…”