Mechanisms of neurocognitive dysfunction and therapeutic considerations in tuberous sclerosis complex

Current Opinion in Neurology

Volumn 24, Issue 2, 2011, Pages 106-113

  Tsai, Peter ^a   Sahin, Mustafa ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b CLSB 13074 ^*  (United States)

Author keywords

autism; DTI; mTOR; translation

Indexed keywords

EVEROLIMUS; PEPTIDES AND PROTEINS; RAPAMYCIN; TUBERIN; TUBEROUS SCLEROSIS 1 PROTEIN; UNCLASSIFIED DRUG;

ANGIOMYOLIPOMA; ARTICLE; ASTROCYTOMA; COGNITIVE DEFECT; CYTOGENETICS; DEMYELINATION; DRUG TARGETING; GENE MUTATION; HAPLOTYPE; HETEROZYGOSITY LOSS; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LYMPHANGIOLEIOMYOMATOSIS; NERVE FIBER; NEUROIMAGING; NEUROLOGIC DISEASE; NEUROPATHOLOGY; NONHUMAN; PATHOGENESIS; PHENOTYPE; RHABDOMYOMA; SIGNAL TRANSDUCTION; SUBEPENDYMAL GIANT CELL ASTROCYTOMA; TUBEROUS SCLEROSIS; UNSPECIFIED SIDE EFFECT;

ABNORMALITIES, MULTIPLE; ANIMALS; COGNITION DISORDERS; DISEASE MODELS, ANIMAL; HUMANS; NEURONS; PROTEINS; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS;

EID: 79953030273     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/WCO.0b013e32834451c4     Document Type: Article

References (66)

1. Huang J, Manning BD. The TSC1 -TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008;412:179-190. (Pubitemid 351758225)
2. Asato MR, Hardan AY. Neuropsychiatric problems in tuberous sclerosis complex. J Child Neurol 2004;19:241-249. (Pubitemid 38660205)
3. Goodman M, Lamm SH, Engel A, et al. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol 1997;12:85-90. (Pubitemid 27118428)
4. Jambaque I, Cusmai R, Curatolo P, et al. Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings. Dev Med Child Neurol 1991;33:698-705.
5. Jansen FE, Vincken KL, Algra A, et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition. Neurology 2008;70:916-923. (Pubitemid 351430755)
6. Bolton PF, Park RJ, Higgins JN, et al. Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 2002;125:1247-1255. (Pubitemid 34587134)
7. Eluvathingal TJ, Behen ME, Chugani HT, et al. Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates. J Child Neurol 2006;21:846-851. (Pubitemid 46099270)
8. Weber AM, Egelhoff JC, McKellop JM, Franz DN. Autism and the cerebellum: evidence from tuberous sclerosis. J Autism Dev Disord 2000;30:511-517. (Pubitemid 32183333)
9. Gama HP, da Rocha AJ, Valerio RM, et al. Hippocampal abnormalities in an MR imaging series of patients with tuberous sclerosis. AJNR Am J Neuroradiol 2010;31:1059-1062.
10. Ertan G, Arulrajah S, Tekes A, et al. Cerebellar abnormality in children and young adults with tuberous sclerosis complex: MR and diffusion weighted imaging findings. J Neuroradiol 2010;37:231-238.
11. Asano E, Chugani DC, Muzik O, et al. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology 2001;57:1269-1277. (Pubitemid 32947387)
12. Widjaja E, Simao G, Mahmoodabadi SZ, et al. Diffusion tensor imaging identifies changes in normal-appearing white matter within the epileptogenic zone in tuberous sclerosis complex. Epilepsy Res 2010;89:246-253.
13. Garaci FG, Floris R, Bozzao A, et al. Increased brain apparent diffusion coefficient in tuberous sclerosis. Radiology 2004;232:461-465. (Pubitemid 38971287)
14. Peng SS, Lee WT, Wang YH, Huang KM. Cerebral diffusion tensor images in children with tuberous sclerosis: a preliminary report. Pediatr Radiol 2004;34:387-392. (Pubitemid 38701988)
15. Krishnan ML, CommowickO, JesteSS, et al. Diffusion features of white matter in tuberous sclerosis with tractography. Pediatr Neurol 2010;42:101-106.
16. Simao G, Raybaud C, Chuang S, et al. Diffusion tensor imaging of commis- sural and projection white matter in tuberous sclerosis complex and correlation with tuber load. AJNR Am J Neuroradiol 2010;31:1273-1277.
17. Luat AF, Makki M, Chugani HT. Neuroimaging in tuberous sclerosis complex. Curr Opin Neurol 2007;20:142-150. (Pubitemid 46411498)
18. Arulrajah S, Ertan G, Jordan L, et al. Magnetic resonance imaging and diffusion-weighted imaging of normal-appearing white matter in children and young adults with tuberous sclerosis complex. Neuroradiology 2009;51:781-786.
19. Makki MI, Chugani DC, Janisse J, Chugani HT. Characteristics of abnormal diffusivity in normal-appearing white matter investigated with diffusion tensor MR imaging in tuberous sclerosis complex. AJNR Am J Neuroradiol 2007;28:1662-1667. (Pubitemid 47598136)
20. Niida Y, Stemmer-Rachamimov AO, Logrip M, et al. Survey of somatic mutations in tuberous sclerosis complex (TSC) hamartomas suggests different genetic mechanisms for pathogenesis of TSC lesions. Am J Hum Genet 2001;69:493-503. (Pubitemid 32777689)
21. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006;355:1345-1356.
22. Crino PB, Aronica E, Baltuch G, Nathanson KL. Biallelic TSC gene inactivation in tuberous sclerosis complex. Neurology 2010;74:1716-1723.
23. Qin W, Chan JA, Vinters HV, et al. Analysis of TSC cortical tubers by deepsequencing of TSC1, TSC2 and KRAS demonstrates that small second-hit mutations in these genes are rare events. Brain Pathol 2010;20:1096-1105.
24. Waltereit R, Welzl H, Dichgans J, et al. Enhanced episodic-like memory and kindling epilepsy in a rat model of tuberous sclerosis. J Neurochem 2006;96:407-413.
25. Waltereit R, Japs B, Schneider M, et al. Epilepsy and Tsc2 haploinsufficiency lead to autistic-like social deficit behaviors in rats. Behav Genet 2010 [Epub ahead of print].
26. +/~ mice in the absence of cerebral lesions and seizures. Ann Neurol 2007;62:648-655.
27. Onda H, Lueck A, Marks PW, et al. Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest 1999;104:687-695. (Pubitemid 29536354)
28. +/~ mouse model of tuberous sclerosis. Nat Med 2008;14:843-848.
29. Young DM, Schenk AK, Yang SB, et al. Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism. Proc Natl Acad Sci USA 2010;107:11074-11079.
30. Nie D, Di Nardo A, Han JM, et al. Tsc2-Rheb signaling regulates EphA-mediated axon guidance. Nat Neurosci 2010;13:163-172.
31. Govindarajan B, Brat DJ, Csete M, et al. Transgenic expression of dominant negative tuberin through a strong constitutive promoter results in a tissue-specific tuberous sclerosis phenotype in the skin and brain. J Biol Chem 2005;280:5870-5874. (Pubitemid 40280069)
32. Ehninger D, Silva AJ. Increased levels of anxiety-related behaviors in a Tsc2 dominant negative transgenic mouse model of tuberous sclerosis. Behav Genet 2010 [Epub ahead of print].
33. Uhlmann EJ, Wong M, Baldwin RL, et al. Astrocyte-specific TSC1 conditional knockout mice exhibit abnormal neuronal organization and seizures. Ann Neurol 2002;52:285-296. (Pubitemid 35001494)
34. Wong M, Ess KC, Uhlmann EJ, et al. Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model. Ann Neurol 2003;54:251-256. (Pubitemid 36909626)
35. Xu L, Zeng LH, Wong M. Impaired astrocytic gap junction coupling and potassium buffering in a mouse model of tuberous sclerosis complex. Neurobiol Dis 2009;34:291-299.
36. Zeng LH, Bero AW, Zhang B, et al. Modulation of astrocyte glutamate transporters decreases seizures in a mouse model of tuberous sclerosis complex. Neurobiol Dis 2010;37:764-771.
37. Zeng LH, Ouyang Y, Gazit V, et al. Abnormal glutamate homeostasis and impaired synaptic plasticity and learning in a mouse model of tuberous sclerosis complex. Neurobiol Dis 2007;28:184-196. (Pubitemid 47615457)
38. Meikle L, Talos DM, Onda H, et al. A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci 2007;27:5546-5558. (Pubitemid 350021088)
39. Way SW, McKenna J 3rd, Mietzsch U, et al. Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse. Hum Mol Genet 2009;18:1252-1265.
40. Kobayashi T, Minowa O, Kuno J, et al. Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice. Cancer Res 1999;59:1206-1211. (Pubitemid 29136248)
41. Kobayashi T, Minowa O, Sugitani Y, et al. A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice. Proc Natl Acad Sci USA 2001;98:8762-8767. (Pubitemid 32678101)
42. Ehninger D,SanoY,deVries PJ, et al. Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Mol Psychiatry 2010 [Epub ahead of print].
43. Onda H, Crino PB, Zhang H, et al. Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway. Mol Cell Neurosci 2002;21:561-574. (Pubitemid 36062714)
44. Choi YJ, Di Nardo A, Kramvis I, et al. Tuberous sclerosis complex proteins control axon formation. Genes Dev 2008;22:2485-2495.
45. Tavazoie SF, Alvarez VA, Ridenour DA, et al. Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci 2005;8:1727-1734. (Pubitemid 41683201)
46. Cajigas IJ, Will T, Schuman EM. Protein homeostasis and synaptic plasticity. EMBO J 2010;29:2746-2752.
47. Haddad LA, Smith N, Bowser M, et al. The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton. J Biol Chem 2002;277:44180-44186. (Pubitemid 36157848)
48. Li YH, Werner H, Puschel AW. Rheb and mTOR regulate neuronal polarity through Rap1B. J Biol Chem 2008;283:33784-33792.
49. Morita T, Sobue K. Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway. J Biol Chem 2009;284:27734-27745.
50. Meikle L, Pollizzi K, Egnor A, et al. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci 2008;28:5422-5432.
51. Zeng LH, Xu L, Gutmann DH, Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol 2008;63:444-453. (Pubitemid 351614710)
52. Franz DN, Leonard J, Tudor C, et al. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 2006;59:490-498. (Pubitemid 43358069)
53. Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 2010;363:1801-1811.
54. Lee PS, Tsang SW, Moses MA, et al. Rapamycin-insensitive up-regulation of MMP2 and other genes in tuberous sclerosis complex 2-deficient lymphan-gioleiomyomatosis-like cells. Am J Respir Cell Mol Biol 2010;42:227-234.
55. Lee N, Woodrum CL, Nobil AM, et al. Rapamycin weekly maintenance dosing and the potential efficacy of combination sorafenib plus rapamycin but not atorvastatin or doxycycline in tuberous sclerosis preclinical models. BMC Pharmacol 2009;9:8.
56. Kalender A, Selvaraj A, Kim SY, et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab 2010;11:390-401.
57. Sini P, James D, Chresta C, Guichard S. Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells. Autophagy 2010;6:553-554.
58. Lin CJ, Robert F, Sukarieh R, et al. The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling. Cancer Res 2010;70:3199-3208.
59. Liu M, Wilk SA, Wang A, et al. Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR. J Biol Chem 2010;285:36387-36394.
60. Balgi AD, Fonseca BD, Donohue E, et al. Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling. PLoS One 2009;4:e7124.
61. Richard DJ, Verheijen JC, Zask A. Recent advances in the development of selective, ATP-competitive inhibitors of mTOR. Curr Opin Drug Discov Devel 2010;13:428-440.
62. Johannessen CM, Johnson BW, Williams SM, et al. TORC1 is essential for NF1-associated malignancies. Curr Biol 2008;18:56-62.
63. Gross C, NakamotoM, YaoX, et al. Excess phosphoinositide3-kinasesubunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J Neurosci 2010;30:10624-10638.
64. Sharma A, Hoeffer CA, Takayasu Y, et al. Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 2010;30:694-702.
65. Kwon CH, Luikart BW, Powell CM, et al. Pten regulates neuronal arborization and social interaction in mice. Neuron 2006;50:377-388.
66. Butler MG, Dasouki MJ, Zhou XP, et al. Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 2005;42:318-321. (Pubitemid 40523954)