Naslov
Lipid raft-integrated protein markers in exosomes. Association with protein sorting in neurodegenerative diseases

Autori
Puertas-Avendaño, Ricardo ; Zjalić, Milorad ; Heffer, Marija ; Marin, R.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the XXXIX Congress of the Spanish Society of Physiological Sciences (SECF), 18-21 September 2018, Cádiz, Spain / Lostao, M.P. ; Moreno Aliaga, M.J. - : Springer, 2018, 44-45

Skup
39th Congress of the Spanish Society of Physiological Sciences (SECF)

Mjesto i datum
Cadiz, Španjolska, 18.09.2018. - 21.09.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Lipid rafts ; exosomes ; proteinopathies

Sažetak
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 in 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 disease (PD), exosomes importantly contribute to propagating neurotoxic aberrant protein aggregates and misfolded markers, thus contributing to increase the neurotoxicity impact. Recent evidence has emonstrated that some of the typical hallmarks of AD and PD, i.e. amyloid- beta peptide (Aβ)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 A β and α-Syn oligomerization are also involved in the propagation of toxic aggregates. We demonstrate here, using human neuroblastoma SHSY-5Y cells, that Aβ and α -Syn markers are abundantly secreted specifically in 30-50 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, these <50 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. These experiments were performed by using SHSY-5Y cells previously differentiated with retinoic acid and Phorbol 12-myristate 13- acetate. SHSY-5Y cells were processed for immunofluorescence and confocal microscopy. Further analyses were performed by immunogoldand transmission electron microscopy using specific antibodies Abstract directed to the different protein markers. 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-cell propagation of aberrant molecular species that may enhance the neuropathological progression. Supported by SAF2014-52582-R and SAF2017-84454-R. References from the Research Group: 1. Marin R, et al. Curr Alzheimer Res. 2016 ; 13(9):973-84. 2. Marin R, et al. Neurobiol Aging. 2017 ; 49:52- 59. 3. Díaz M, et al. Neurobiol Aging. 2018 ; 67:42-52. Lipid rafts, exosomes, proteinopathy

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti

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