Lipid rafts, synaptic transmission and plasticity: Impact in age-related neurodegenerative diseases

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

“…MLRs have been implicated in various physiological cellular processes, such as protein membrane trafficking and signal transduction, and they have been demonstrated to play roles in synaptic plasticity and contribute to neuropathologies, such as Alzheimer's disease, Parkinson's disease, and Huntington disease (Hanzal-Bayer, Hancock, 2007;Karasinska, Hayden, 2011;Korade, Kenworthy, 2008;Sebastião et al, 2013;Simons, Toomre, 2000). Cholesterol is a key component of MLRs, as its depletion disrupts MLRs and leads to synaptic dysfunction or loss of synapses (Fielding, Fielding, 2003;Korade, Kenworthy, 2008;Sebastião et al, 2013). Cholesterol is responsible for MLRs maintenance in a liquid-ordered phase (Marwali et al, 2003).…”

“…MLRs have been proposed to function as platforms that allow the local accumulation of raftsassociated proteins, promoting interactions among protein complexes and modulating neurotransmitter signaling (Allen, Halverson-Tamboli, Rasenick, 2007;Resh, 2004). Accumulating evidence indicates that the precise localization of neurotransmitter receptors, transporters, ion channels, and other synaptic proteins in MLRs can be regulated by cholesterol and this regulation is critical for synaptic plasticity (Allen, Halverson-Tamboli, Rasenick, 2007;Sebastião et al, 2013). Due to its impact on cholesterol synthesis and protein modification, SIM perturbs the composition and properties of MLRs (van der Most et al, 2009).…”

Alzheimer’s Disease Risk Genes and Lipid Regulators

“…It also plays a key role in cell growth, viability, and synaptic plasticity [37]. Brain cholesterol represents 25% of the total amount of cholesterol in the human body.…”

Molecular and structural bases for postsynaptic signal processing: interaction between postsynaptic density and postsynaptic membrane rafts

“…Accumulating evidence demonstrates that various types of neurotransmitter receptors other than the Glu receptor, γ-aminobutyric acid A (GABA A ) receptor, and glycine receptor are also codistributed with membrane rafts. 41 Raft-associated neurotransmitter receptors include the GABA B receptor (metabotropic), 42 nicotinic acetylcholine receptor (nAChR), 43 metabotropic AChR, 44 dopamine D 1 receptor, 45 and serotonin receptors (5-HT 1-7 ), as well as 5-HT transporters 46 and purinergic receptors, both ionotropic P2X and metabotropic P2Y. 46 Additional evidence that supports raft association of non-type I synapses includes palmitoylation of GABA A receptors, 47 effects of cholesterol depletion on GABA A receptor β2/3 subunit cluster distribution, 48 and the presence and roles of membrane rafts at neuromuscular junctions.…”

“…48,[59][60][61][62][63][64] Presynaptic roles of membrane rafts are evident by the presence of proteins deeply linked to neurotransmitter-release mechanisms (soluble N-ethylmaleimide-sensitive factor attachment protein-receptor (SNARE) proteins, neuronal Ca 2+ sensor 1 (NCS-1), and voltage-dependent Ca 2+ channel Ca v 2.1) in the DRM, and by the impairment of synaptic release associated with decreased cholesterol level. 46 Ganglioside, a main constituent of membrane rafts, is also enriched in the brain 65 and plays a major role in cell-cell recognition and cell signaling. 66,67 Ganglioside is involved in the maintenance of neural function and plasticity, such as membrane raft-dependent neuritogenesis in Neuro-2a cells.…”