Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Incretin analogues that have been developed to treat type 2 diabetes hold promise as a novel treatment strategy for Alzheimer's disease
AU - Hölscher, Christian
PY - 2010/6
Y1 - 2010/6
N2 - Analogues of the incretins Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic peptide (GIP) have been developed to treat type 2 diabetes mellitus. They are protease resistant and have a longer biological half life than the native peptides. Some of these novel analogues can cross the blood-brain barrier, have neuroprotective effects, activate neuronal stem cells in the brain, and can improve cognition. The receptors for GIP and GLP-1 are expressed in neurons, and both GIP and GLP-1 are expressed and released as transmitters by neurons. GIP analogues such as DAla(2)GIP and GLP-1 analogues such as liraglutide enhance synaptic plasticity in the brain and also reverse the betaamyloid induced impairment of synaptic plasticity. In mouse models of Alzheimer's disease, GLP-1 analogues Val(8)GLP-1 and liraglutide prevent memory impairment and the block of synaptic plasticity in the brain. Since two GLP- 1 analogues exendin-4 (Exenatide, Byetta) and liraglutide (Victoza) are already on the market as treatments for Type 2 diabetes, and others are in late stage clinical trials, these drugs show promise as treatments for neurodegenerative diseases such as Alzheimer's disease. Currently, there are three patents covering native GLP-1 and different GLP-1 analogues and one patent for the use of GIP and different GIP analogues for the treatment of neurodegenerative diseases.
AB - Analogues of the incretins Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic peptide (GIP) have been developed to treat type 2 diabetes mellitus. They are protease resistant and have a longer biological half life than the native peptides. Some of these novel analogues can cross the blood-brain barrier, have neuroprotective effects, activate neuronal stem cells in the brain, and can improve cognition. The receptors for GIP and GLP-1 are expressed in neurons, and both GIP and GLP-1 are expressed and released as transmitters by neurons. GIP analogues such as DAla(2)GIP and GLP-1 analogues such as liraglutide enhance synaptic plasticity in the brain and also reverse the betaamyloid induced impairment of synaptic plasticity. In mouse models of Alzheimer's disease, GLP-1 analogues Val(8)GLP-1 and liraglutide prevent memory impairment and the block of synaptic plasticity in the brain. Since two GLP- 1 analogues exendin-4 (Exenatide, Byetta) and liraglutide (Victoza) are already on the market as treatments for Type 2 diabetes, and others are in late stage clinical trials, these drugs show promise as treatments for neurodegenerative diseases such as Alzheimer's disease. Currently, there are three patents covering native GLP-1 and different GLP-1 analogues and one patent for the use of GIP and different GIP analogues for the treatment of neurodegenerative diseases.
KW - Alzheimer Disease
KW - Amino Acid Sequence
KW - Animals
KW - Blood-Brain Barrier
KW - Diabetes Mellitus, Type 2
KW - Gastric Inhibitory Polypeptide
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Incretins
KW - Models, Neurological
KW - Molecular Sequence Data
KW - Neuroprotective Agents
KW - Patents as Topic
U2 - 10.2174/157488910791213130
DO - 10.2174/157488910791213130
M3 - Journal article
C2 - 20337586
VL - 5
SP - 109
EP - 117
JO - Recent Patents on CNS Drug Discovery
JF - Recent Patents on CNS Drug Discovery
SN - 2212-3954
IS - 2
ER -