PMID- 35326535
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220329
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 6
DP  - 2022 Mar 8
TI  - Occurrence of Total and Proteinase K-Resistant Alpha-Synuclein in Glioblastoma 
      Cells Depends on mTOR Activity.
LID - 10.3390/cancers14061382 [doi]
LID - 1382
AB  - Alpha-synuclein (alpha-syn) is a protein considered to be detrimental in a number of 
      degenerative disorders (synucleinopathies) of which alpha-syn aggregates are 
      considered a pathological hallmark. The clearance of alpha-syn strongly depends on 
      autophagy, which can be stimulated by inhibiting the mechanistic target of 
      rapamycin (mTOR). Thus, the overexpression of mTOR and severe autophagy 
      suppression may produce alpha-syn accumulation, including the proteinase K-resistant 
      protein isoform. Glioblastoma multiforme (GBM) is a lethal brain tumor that 
      features mTOR overexpression and severe autophagy inhibition. Cell pathology in 
      GBM is reminiscent of a fast, progressive degenerative disorder. Therefore, the 
      present work questions whether, as is analogous to neurons during degenerative 
      disorders, an overexpression of alpha-syn occurs within GBM cells. A high amount of 
      alpha-syn was documented in GBM cells via real-time PCR (RT-PCR), Western blotting, 
      immunohistochemistry, immuno-fluorescence, and ultrastructural stoichiometry, 
      compared with the amount of beta- and gamma-synucleins and compared with the amount of 
      alpha-syn counted within astrocytes. The present study indicates that (i) alpha-syn is 
      overexpressed in GBM cells, (ii) alpha-syn expression includes a proteinase-K 
      resistant isoform, (iii) alpha-syn is dispersed from autophagy-like vacuoles to the 
      cytosol, (iv) alpha-syn overexpression and cytosol dispersion are mitigated by 
      rapamycin, and (v) the alpha-syn-related GBM-like phenotype is mitigated by silencing 
      the SNCA gene.
FAU - Ryskalin, Larisa
AU  - Ryskalin L
AUID- ORCID: 0000-0003-3150-1863
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
FAU - Ferese, Rosangela
AU  - Ferese R
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
FAU - Morucci, Gabriele
AU  - Morucci G
AUID- ORCID: 0000-0003-0518-2184
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
FAU - Biagioni, Francesca
AU  - Biagioni F
AUID- ORCID: 0000-0003-3566-4889
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
FAU - Busceti, Carla L
AU  - Busceti CL
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
FAU - Michetti, Fabrizio
AU  - Michetti F
AUID- ORCID: 0000-0003-2546-0532
AD  - Departmentof Neuroscience, Universita Cattolica del Sacro Cuore, Largo Francesco 
      Vito 1, 00168 Rome, Italy.
AD  - IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) San Raffaele 
      Scientific Institute, Universita Vita-Salute San Raffaele, Via Olgettina 6, 20121 
      Milan, Italy.
FAU - Lenzi, Paola
AU  - Lenzi P
AUID- ORCID: 0000-0002-4734-8798
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
FAU - Frati, Alessandro
AU  - Frati A
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
AD  - Neurosurgery Division, Human Neurosciences Department, Sapienza University, 00135 
      Roma, Italy.
FAU - Fornai, Francesco
AU  - Fornai F
AUID- ORCID: 0000-0002-3883-5084
AD  - Department of Translational Research and New Technologies in Medicine and 
      Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
AD  - Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via 
      Atinense 18, 86077 Pozzilli, Italy.
LA  - eng
GR  - Ricerca Corrente 2021/Ministero della Salute/
PT  - Journal Article
DEP - 20220308
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8946689
OTO - NOTNLM
OT  - autophagy vacuoles
OT  - cell-clearing systems
OT  - glioblastoma multiforme
OT  - mechanistic target of rapamycin
OT  - qRT-PCR
OT  - siRNA
OT  - synucleins
OT  - transmission electron microscopy
COIS- The authors declare no conflict of interest.
EDAT- 2022/03/26 06:00
MHDA- 2022/03/26 06:01
PMCR- 2022/03/08
CRDT- 2022/03/25 01:01
PHST- 2022/01/11 00:00 [received]
PHST- 2022/03/01 00:00 [revised]
PHST- 2022/03/07 00:00 [accepted]
PHST- 2022/03/25 01:01 [entrez]
PHST- 2022/03/26 06:00 [pubmed]
PHST- 2022/03/26 06:01 [medline]
PHST- 2022/03/08 00:00 [pmc-release]
AID - cancers14061382 [pii]
AID - cancers-14-01382 [pii]
AID - 10.3390/cancers14061382 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Mar 8;14(6):1382. doi: 10.3390/cancers14061382.