Extracellular propagation of lipid raft molecular species involved in Parkinson’s disease neurodegeneration. In: Closer look at neurotoxicity (CROSBI ID 68313)
Prilog u knjizi | ostalo
Podaci o odgovornosti
Pereda, Daniel ; Puertas- Avendaño, Ricardo ; Zjalić, Milorad ; Heffer , Marija ; Gonzalez-Marrero, Ibrahim ; González-Gőmez, Miriam ; Diaz, Mario ; Marin, Raquel
engleski
Extracellular propagation of lipid raft molecular species involved in Parkinson’s disease neurodegeneration. In: Closer look at neurotoxicity
Exosomes are small membrane nanovesicles, generally 50 to 90 nm size, secreted by cells upon fusion with the cell membrane. When released, exosomes can propagate molecular content to other cells over long distances. In neurons, these nanovesicles contribute to regulating neuronal development, plasticity and regeneration. Related to neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), exosomes importantly contribute to propagating neurotoxic aberrant protein aggregates and misfolded markers, thus contributing to increase the neurotoxicity impact. Recent evidence has demonstrated that some of the typical hallmarks of AD and PD, i.e., amyloid- beta peptide (A) and α-synuclein (α-Syn) associate with lipid markers integrated in lipid raft membrane microdomains as part of their mechanisms of pathological self-aggregation. Lipid rafts are laterally organized structures within cell membranes based on a particular lipid composition enriched in gangliosides, sphingolipids and cholesterol. Our previous work has extensively demonstrated that these membrane microstructures are involved in AD, PD and other synucleopathies. Indeed, different lipid species such as ganglioside GM1 and cholesterol highly enriched in lipid rafts, known to enhance Aand α-Syn oligomerization are also involved in the propagation of toxic aggregates. We demonstrate here that Aand α-Syn markers are abundantly secreted specifically in 30-90 nm size vesicles. Other protein raft markers known to participate in AD pathology, such as flotillin-1 and the voltage dependent anion channel (VDAC) are also found in these exosomes. Noticeably, this 30-90 nm subclass shows a high content of ganglioside GM1, as an indicative of the potential involvement of this lipid class in toxic protein markers propagation. Overall, these results suggest that lipid rafts are involved not only in the mechanisms of conformational transition and oligomerization of toxic protein markers but also in the cell to cell propagation of aberrant molecular species that may enhance the neuropathological progression.
nanovesicles ; exosomes ; lipid rafts ; alpha-synuclein ; amyloid beta peptide ; voltage-dependent anion channel 1 ; Alzheimer’s disease ; Parkinson’s disease
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Podaci o prilogu
53-84.
objavljeno
Podaci o knjizi
A Closer Look at Neurotoxicity
Gokol, Krishna
New York (NY): Nova Science Publishers
2020.
978-1-53616-591-3