PMID- 21787319
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20151119
IS  - 1470-8752 (Electronic)
IS  - 0300-5127 (Linking)
VI  - 39
IP  - 4
DP  - 2011 Aug
TI  - Diabetes as a risk factor for Alzheimer's disease: insulin signalling impairment 
      in the brain as an alternative model of Alzheimer's disease.
PG  - 891-7
LID - 10.1042/BST0390891 [doi]
AB  - Surprisingly little is known about the mechanisms that trigger the onset of AD 
      (Alzheimer's disease) in sporadic forms. A number of risk factors have been 
      identified that may shed light on the mechanisms that may trigger or facilitate 
      the development of AD. Recently, T2DM (Type 2 diabetes mellitus) has been 
      identified as a risk factor for AD. A common observation for both conditions is 
      the desensitization of insulin receptors in the brain. Insulin acts as a growth 
      factor in the brain and is neuroprotective, activates dendritic sprouting, 
      regeneration and stem cell proliferation. The impairment of this important growth 
      factor signal may facilitate the development of AD. Insulin as well as other 
      growth factors have shown neuroprotective properties in preclinical and clinical 
      trials. Several drugs have been developed to treat T2DM, which re-sensitize 
      insulin receptors and may be of use to prevent neurodegenerative processes in the 
      brain. In particular, the incretins GLP-1 (glucagon-like peptide-1) and GIP 
      (glucose-dependent insolinotropic polypeptide) are hormones that re-sensitize 
      insulin signalling. Incretins also have similar growth-factor-like properties as 
      insulin and are neuroprotective. In mouse models of AD, GLP-1 receptor agonists 
      reduce amyloid plaque formation, reduce the inflammation response in the brain, 
      protect neurons from oxidative stress, induce neurite outgrowth, and protect 
      synaptic plasticity and memory formation from the detrimental effects caused by 
      beta-amyloid production and inflammation. Other growth factors such as BDNF 
      (brain-derived neurotrophic factor), NGF (nerve growth factor) or IGF-1 
      (insulin-like growth factor 1) also have shown a range of neuroprotective 
      properties in preclinical studies. These results show that these growth factors 
      activate similar cell signalling mechanisms that are protective and regenerative, 
      and suggest that the initial process that may trigger the cascade of 
      neurodegenerative events in AD could be the impairment of growth factor 
      signalling such as early insulin receptor desensitization.
FAU - Holscher, Christian
AU  - Holscher C
AD  - School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 
      1SA, UK. christian_holscher@mac.com
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Soc Trans
JT  - Biochemical Society transactions
JID - 7506897
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glp1r protein, mouse)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Insulin)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Glucagon)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
SB  - IM
MH  - Alzheimer Disease/drug therapy/*etiology
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Disease Models, Animal
MH  - Gastric Inhibitory Polypeptide/metabolism
MH  - Glucagon-Like Peptide 1/analogs & derivatives/metabolism/therapeutic use
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Humans
MH  - Insulin/*metabolism/therapeutic use
MH  - Intercellular Signaling Peptides and Proteins/therapeutic use
MH  - Mice
MH  - Mice, Transgenic
MH  - Neuroprotective Agents/therapeutic use
MH  - Receptors, Glucagon/agonists
MH  - *Signal Transduction
EDAT- 2011/07/27 06:00
MHDA- 2011/11/16 06:00
CRDT- 2011/07/27 06:00
PHST- 2011/07/27 06:00 [entrez]
PHST- 2011/07/27 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
AID - BST0390891 [pii]
AID - 10.1042/BST0390891 [doi]
PST - ppublish
SO  - Biochem Soc Trans. 2011 Aug;39(4):891-7. doi: 10.1042/BST0390891.