scholarly journals Linking tuberous sclerosis complex, excessive mTOR signaling, and age-related neurodegeneration: a new association between TSC1 mutation and frontotemporal dementia

2017 ◽  
Vol 134 (5) ◽  
pp. 813-816 ◽  
Author(s):  
Nicholas T. Olney ◽  
Carolina Alquezar ◽  
Eliana Marisa Ramos ◽  
Alissa L. Nana ◽  
Jamie C. Fong ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Frontotemporal Dementia ◽  
Tuberous Sclerosis Complex ◽  
Mtor Signaling ◽  
Age Related ◽  
New Association

scholarly journals Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb

2003 ◽  
Vol 13 (15) ◽  
pp. 1259-1268 ◽  
Author(s):  
Andrew R Tee ◽  
Brendan D Manning ◽  
Philippe P Roux ◽  
Lewis C Cantley ◽  
John Blenis
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Protein Complex ◽  
Mtor Signaling ◽  
Gene Products ◽  
Gtpase Activating Protein

scholarly journals Regulation of mast cell survival and function by tuberous sclerosis complex 1

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3306-3314 ◽  
Author(s):  
Jinwook Shin ◽  
Hongjie Pan ◽  
Xiao-Ping Zhong
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Survival ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Cell Activation ◽  
Cytokine Production ◽  
Mast Cell Degranulation ◽  
Mtor Signaling ◽  
Mast Cell Activation

Abstract Mast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR signaling in mast cells downstream of FcεRI and c-Kit, and differentially controls mast cell degranulation and cytokine production. TSC1-deficiency results in impaired mast cell degranulation, but enhanced cytokine production in vitro and in vivo after FcεRI engagement. Furthermore, TSC1 is critical for mast cell survival through multiple pathways of apoptosis including the down-regulation of p53, miR-34a, reactive oxygen species, and the up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical regulator of mast cell activation and survival, suggesting the manipulation of the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated diseases.

scholarly journals Fetal Brain mTOR Signaling Activation in Tuberous Sclerosis Complex

2012 ◽  
Vol 24 (2) ◽  
pp. 315-327 ◽  
Author(s):  
Victoria Tsai ◽  
Whitney E. Parker ◽  
Ksenia A. Orlova ◽  
Marianna Baybis ◽  
Anthony W.S. Chi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Fetal Brain ◽  
Mtor Signaling ◽  
Signaling Activation

scholarly journals mTOR Signaling and Neural Stem Cells: The Tuberous Sclerosis Complex Model

2018 ◽  
Vol 19 (5) ◽  
pp. 1474 ◽  
Author(s):  
Alice Polchi ◽  
Alessandro Magini ◽  
Danila Meo ◽  
Brunella Tancini ◽  
Carla Emiliani
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Complex Model ◽  
Mtor Signaling

scholarly journals Tuberous sclerosis complex–mediated mTORC1 overactivation promotes age-related hearing loss

2018 ◽  
Vol 128 (11) ◽  
pp. 4938-4955 ◽  
Author(s):  
Xiaolong Fu ◽  
Xiaoyang Sun ◽  
Linqing Zhang ◽  
Yecheng Jin ◽  
Renjie Chai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Silent gonadotroph pituitary neuroendocrine tumor in a patient with tuberous sclerosis complex: evaluation of a possible molecular link

2018 ◽  
Vol 2018 ◽  
Author(s):  
Daniela Regazzo ◽  
Marina Paola Gardiman ◽  
Marily Theodoropoulou ◽  
Carla Scaroni ◽  
Gianluca Occhi ◽  
...  
Keyword(s):  
Cell Viability ◽  
Tuberous Sclerosis ◽  
Neuroendocrine Tumors ◽  
Tuberous Sclerosis Complex ◽  
Mtor Signaling ◽  
List Type ◽  
Primary Cells ◽  
Endoscopic Neurosurgery ◽  
Cellular Models

Summary Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem hereditary cutaneous condition, characterized by multiple hamartomas. In rare cases, pituitary neuroendocrine tumors (PitNETs) have been described in patients with TSC, but the causal relationship between these two diseases is still under debate. TSC is mostly caused by mutations of two tumor suppressor genes, encoding for hamartin (TSC1) and tuberin (TSC2), controlling cell growth and proliferation. Here, we present the case of a 62-year-old Caucasian woman with TSC and a silent gonadotroph PitNET with suprasellar extension, treated with transsphenoidal endoscopic neurosurgery with complete resection. Therapeutic approaches based on mTOR signaling (i.e. everolimus) have been successfully used in patients with TSC and tested in non-functioning PitNET cellular models with promising results. Here, we observed a reduction of cell viability after an in vitro treatment of PitNET’s derived primary cells with everolimus. TSC analysis retrieved no disease-associated variants with the exception of the heterozygous intronic variant c.4006-71C>T found in TSC2: the computational tools predicted a gain of a new splice site with consequent intron retention, not confirmed by an in vitro analysis of patient’s lymphocyte-derived RNA. Further analyses are therefore needed to provide insights on the possible mechanisms involving the hamartin-tuberin complex in the pathogenesis of pituitary adenomas. However, our data further support previous observations of an antiproliferative effect of everolimus on PitNET. Learning points: Pituitary neuroendocrine tumors (PitNET) in patients with tuberous sclerosis complex (TSC) are rare: only few cases have been reported in literature. Therapeutic approach related to mTOR signaling, such as everolimus, may be used in some patients with PitNETs as well as those with TSC. We reported a woman with both non-secreting PitNET and TSC; PitNET was surgically removed and classified as a silent gonadotroph tumor. Everolimus treatment in PitNET’s-derived primary cells revealed a significant decrease in cell viability. Considering our case and available evidence, it is still unclear whether a PitNET is a part of TSC or just a coincidental tumor.

Predictors of Efficacy in Patients with Adjunctive Everolimus Therapy for Treatment-Resistant Seizures Associated with Tuberous Sclerosis Complex

2017 ◽  
Vol 48 (S 01) ◽  
pp. S1-S45
Author(s):  
G. Wiegand ◽  
T. Polster ◽  
C. Hertzberg ◽  
A. Wiemer-Kruel ◽  
J. French ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Treatment Resistant
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