PMID- 9063586
OWN - NLM
STAT- MEDLINE
DCOM- 19970523
LR  - 20191101
VI  - 23
IP  - 1-2
DP  - 1997 Feb
TI  - Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury 
      responses and Alzheimer's disease.
PG  - 47-61
AB  - beta-Amyloid precursor protein (beta APP), transforming growth factor beta (TGF 
      beta), and tumor necrosis factor-alpha (TNF alpha) are remarkably pleiotropic 
      neural cytokines/neurotrophic factors that orchestrate intricate injury-related 
      cellular and molecular interactions. The links between these three factors 
      include: their responses to injury; their interactive effects on astrocytes, 
      microglia and neurons; their ability to induce cytoprotective responses in 
      neurons; and their association with cytopathological alterations in Alzheimer's 
      disease. Astrocytes and microglia each produce and respond to TGF beta and TNF 
      alpha in characteristic ways when the brain is injured. TGF beta, TNF alpha and 
      secreted forms of beta APP (sAPP) can protect neurons against excitotoxic, 
      metabolic and oxidative insults and may thereby serve neuroprotective roles. On 
      the other hand, under certain conditions TNF alpha and the fibrillogenic amyloid 
      beta-peptide (A beta) derivative of beta APP can promote damage of neuronal and 
      glial cells, and may play roles in neurodegenerative disorders. Studies of 
      genetically manipulated mice in which TGF beta, TNF alpha or beta APP ligand or 
      receptor levels are altered suggest important roles for each factor in cellular 
      responses to brain injury and indicate that mediators of neural injury responses 
      also have the potential to enhance amyloidogenesis and/or to interfere with 
      neuroregeneration if expressed at abnormal levels or modified by strategic point 
      mutations. Recent studies have elucidated signal transduction pathways of TGF 
      beta (serine/threonine kinase cascades), TNF alpha (p55 receptor linked to a 
      sphingomyelin-ceramide-NF kappa B pathway), and secreted forms of beta APP (sAPP; 
      receptor guanylate cyclase-cGMP-cGMP-dependent kinase-K+ channel activation). 
      Knowledge of these signaling pathways is revealing novel molecular targets on 
      which to focus neuroprotective therapeutic strategies in disorders ranging from 
      stroke to Alzheimer's disease.
FAU - Mattson, M P
AU  - Mattson MP
AD  - Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 
      40536-0230, USA. mmattson@aging.coa.uky.edu
FAU - Barger, S W
AU  - Barger SW
FAU - Furukawa, K
AU  - Furukawa K
FAU - Bruce, A J
AU  - Bruce AJ
FAU - Wyss-Coray, T
AU  - Wyss-Coray T
FAU - Mark, R J
AU  - Mark RJ
FAU - Mucke, L
AU  - Mucke L
LA  - eng
GR  - AG11385/AG/NIA NIH HHS/United States
GR  - NS29001/NS/NINDS NIH HHS/United States
GR  - NS30583/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Netherlands
TA  - Brain Res Brain Res Rev
JT  - Brain research. Brain research reviews
JID - 8908638
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Alzheimer Disease/*metabolism/pathology
MH  - Amyloid beta-Protein Precursor/*physiology
MH  - Animals
MH  - Brain/*metabolism/pathology
MH  - Brain Injuries/*metabolism/pathology
MH  - Humans
MH  - Transforming Growth Factor beta/*physiology
MH  - Tumor Necrosis Factor-alpha/*physiology
RF  - 119
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
AID - S0165-0173(96)00014-8 [pii]
AID - 10.1016/s0165-0173(96)00014-8 [doi]
PST - ppublish
SO  - Brain Res Brain Res Rev. 1997 Feb;23(1-2):47-61. doi: 
      10.1016/s0165-0173(96)00014-8.