The role of autophagy in epileptogenesis and in epilepsy-induced neuronal alterations

被引:55
作者
Giorgi, Filippo Sean [1 ]
Biagioni, Francesca [2 ]
Lenzi, Paola [3 ]
Frati, Alessandro [2 ,4 ]
Fornai, Francesco [2 ,3 ]
机构
[1] Univ Pisa, Pisa Univ Hosp, Dept Clin & Expt Med, Neurol Unit, Pisa, Italy
[2] IRCCS INM Neuromed, Pozzilli, Italy
[3] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Pisa, Italy
[4] Univ Roma La Sapienza, I-00185 Rome, Italy
关键词
Autophagosome; Autophagoproteasome; mTOR; Lafora disease; Seizures; Tuberous sclerosis; UBIQUITIN-PROTEASOME SYSTEM; TEMPORAL-LOBE EPILEPSY; FOCAL CORTICAL DYSPLASIA; TUBEROUS SCLEROSIS; MAMMALIAN TARGET; ALPHA-SYNUCLEIN; MOUSE MODEL; CELL-DEATH; MTOR PATHWAY; PROTEIN-DEGRADATION;
D O I
10.1007/s00702-014-1312-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Recent evidence suggests that autophagy alterations are present in a variety of neurological disorders. These range from neurodegenerative diseases to acute neurological insults. Thus, despite a role of autophagy was investigated in a variety of neurological diseases, only recently these studies included epilepsy. This was fostered by the evidence that rapamycin, a powerful autophagy inducer, strongly modulates a variety of seizure models and epilepsies. These findings were originally interpreted as the results of the inhibition exerted by rapamycin on the molecular complex named "mammalian Target of Rapamycin" (mTOR). Recently, an increasing number of papers demonstrated that mTOR inhibition produces a strong activation of the autophagy machinery. In this way, it is now increasingly recognized that what was once defined as mTORpathy in epileptogenesis may be partially explained by abnormalities in the autophagy machinery. The present review features a brief introductory statement about the autophagy machinery and discusses the involvement of autophagy in seizures and epilepsies. An emphasis is posed on evidence addressing both pros and cons making it sometime puzzling and sometime evident, the role of autophagy in the epileptic brain.
引用
收藏
页码:849 / 862
页数:14
相关论文
共 110 条
[1]   Laforin, the most common protein mutated in Lafora disease, regulates autophagy [J].
Aguado, Carmen ;
Sarkar, Sovan ;
Korolchuk, Viktor I. ;
Criado, Olga ;
Vernia, Santiago ;
Boya, Patricia ;
Sanz, Pascual ;
Rodriguez de Cordoba, Santiago ;
Knecht, Erwin ;
Rubinsztein, David C. .
HUMAN MOLECULAR GENETICS, 2010, 19 (14) :2867-2876
[2]   Pten Deletion in Adult Hippocampal Neural Stem/Progenitor Cells Causes Cellular Abnormalities and Alters Neurogenesis [J].
Amiri, Anahita ;
Cho, Woosung ;
Zhou, Jing ;
Birnbaum, Shari G. ;
Sinton, Christopher M. ;
McKay, Renee M. ;
Parada, Luis F. .
JOURNAL OF NEUROSCIENCE, 2012, 32 (17) :5880-5890
[3]  
Anglade P, 1997, HISTOL HISTOPATHOL, V12, P25
[4]   Understanding the interplay between the proteasome pathway and autophagy in response to dual PI3K/mTOR inhibition in myeloma cells is essential for their effective clinical application [J].
Aronson, L. I. ;
Davenport, E. L. ;
Mirabella, F. ;
Morgan, G. J. ;
Davies, F. E. .
LEUKEMIA, 2013, 27 (12) :2397-2403
[5]   mTOR cascade activation distinguishes tubers from focal cortical dysplasia [J].
Baybis, M ;
Yu, J ;
Lee, A ;
Golden, JA ;
Weiner, H ;
McKhann, G ;
Aronica, E ;
Crino, PB .
ANNALS OF NEUROLOGY, 2004, 56 (04) :478-487
[7]   Defining the membrane precursor supporting the nucleation of the phagophore [J].
Bernard, Amelie ;
Klionsky, Daniel J. .
AUTOPHAGY, 2014, 10 (01) :1-2
[8]   Rapamycin suppresses axon sprouting by somatostatin interneurons in a mouse model of temporal lobe epilepsy [J].
Buckmaster, Paul S. ;
Wen, Xiling .
EPILEPSIA, 2011, 52 (11) :2057-2064
[9]   Rapamycin Suppresses Mossy Fiber Sprouting But Not Seizure Frequency in a Mouse Model of Temporal Lobe Epilepsy [J].
Buckmaster, Paul S. ;
Lew, Felicia H. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (06) :2337-2347
[10]   Inhibition of the Mammalian Target of Rapamycin Signaling Pathway Suppresses Dentate Granule Cell Axon Sprouting in a Rodent Model of Temporal Lobe Epilepsy [J].
Buckmaster, Paul S. ;
Ingram, Elizabeth A. ;
Wen, Xiling .
JOURNAL OF NEUROSCIENCE, 2009, 29 (25) :8259-8269