Leptin: a novel therapeutic strategy for Alzheimer's disease.
Adipocyte-derived leptin appears to regulate a number of features defining Alzheimer's disease (AD) at the molecular and physiological level. Leptin has been shown to reduce the amount of extracellular amyloid beta, both in cell culture and animal models, as well as to reduce tau phosphorylation in neuronal cells. Importantly, chronic administration of leptin resulted in a significant improvement in the cognitive performance of transgenic animal models. In AD, weight loss often precedes the onset of dementia and the level of circulating leptin is inversely proportional to the severity of cognitive decline. It is speculated that a deficiency in leptin levels or function may contribute to systemic and CNS abnormalities leading to disease progression. Furthermore, a leptin deficiency may aggravate insulin-controlled pathways, known to be aberrant in AD. These observations suggest that a leptin replacement therapy may be beneficial for these patients.
Tezapsidis
Nikolaos
N
Neurotez, Inc., Bridgewater, New Jersey 08807, USA. ntezapsidis@neurotez.com
Johnston
Jane M
JM
Smith
Mark A
MA
Ashford
J Wesson
JW
Casadesus
Gemma
G
Robakis
Nikolaos K
NK
Wolozin
Benjamin
B
Perry
George
G
Zhu
Xiongwei
X
Greco
Steven J
SJ
Sarkar
Sraboni
S
D000544:Alzheimer Disease / Q000378:metabolism* / Q000628:therapy*; D000818:Animals; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000627:therapeutic use*
D020738:Leptin