PMID- 28186854
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Linking)
VI  - 4
IP  - 5
DP  - 2008 Jul 1
TI  - Adaptive autophagy in Alexander disease-affected astrocytes.
PG  - 701-703
LID - 10.4161/auto.6028 [doi]
AB  - The ubiquitin-proteasome and autophagy-lysosomal pathways are the two main routes 
      of protein and organelle clearance in eukaryotic cells. The proteasome system is 
      responsible for unfolded, short-lived proteins, which precludes the clearance of 
      oligomeric and aggregated proteins, whereas macroautophagy, a process generally 
      referred to as autophagy, mediates mainly the bulk degradation of long-lived 
      cytoplasmic proteins, large protein complexes or organelles.(1) Recently, the 
      autophagy-lysosomal pathway has been implicated in neurodegenerative disorders as 
      an important pathway for the clearance of abnormally accumulated intracellular 
      proteins, such as huntingtin, tau, and mutant and modified alpha-synuclein.(1-6) Our 
      recent study illustrated the induction of adaptive autophagy in response to 
      mutant glial fibrillary acidic protein (GFAP) accumulation in astrocytes, in the 
      brains of patients with Alexander disease (AxD), and in mutant GFAP knock-in 
      mouse brains.(7) This autophagic response is negatively regulated by mammalian 
      target of rapamycin (mTOR). The activation of p38 MAPK by GFAP accumulation is 
      responsible for mTOR inactivation and the induction of autophagy. We also found 
      that the accumulation of GFAP impairs proteasome activity.(8) In this commentary 
      we discuss the potential compensatory relationship between an impaired proteasome 
      and activated autophagy, and propose that the MLK-MAPK (mixed lineage 
      kinase-mitogen-activated protein kinase) cascade is a regulator of this 
      crosstalk. Addendum to: Tang G, Yue Z, Talloczy, Z, Hagemann T, Cho W, Sulzer D, 
      Messing A, Goldman JE. Alexander disease-mutant GFAP accumulation stimulates 
      autophagy through p38 MAPK and mTOR signaling pathways. Hum Mol Genetics 2008; In 
      press.
FAU - Tang, Guomei
AU  - Tang G
FAU - Yue, Zhenyu
AU  - Yue Z
FAU - Talloczy, Zsolt
AU  - Talloczy Z
FAU - Goldman, James E
AU  - Goldman JE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
EDAT- 2008/07/01 00:00
MHDA- 2008/07/01 00:01
CRDT- 2017/02/11 06:00
PHST- 2017/02/11 06:00 [entrez]
PHST- 2008/07/01 00:00 [pubmed]
PHST- 2008/07/01 00:01 [medline]
AID - 10.4161/auto.6028 [doi]
PST - ppublish
SO  - Autophagy. 2008 Jul 1;4(5):701-703. doi: 10.4161/auto.6028.