Hampton DW, Webber DJ, Bilican B, Goedert M, Spillantini MG, Chandran S.
Cell-mediated neuroprotection in a mouse model of human tauopathy.
J Neurosci. 2010 Jul 28;30(30):9973-83.
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The effects of BDNF on neuronal protection and synapse preservation are most impressive, similar to those shown by NGF. As they do not cross the blood-brain barrier (BBB), new methods are tested, such as the stem cell injection or genetic vector transfer of genes that induce increased release of BDNF or NGF. Clearly, that limits the application of these growth factors.
If I may draw attention to the fact that there are other growth factors out there that actually cross the BBB and show exactly the same protective effects: I presented a poster at the meeting on the effects of the incretin GLP-1 analogue Liraglutide. Incretins are well known as novel treatments for type 2 diabetes, but really are growth factors that have numerous other properties in addition to regulating insulin signaling. Liraglutide not only crosses the BBB, but also protects memory in APP/PS1 mice, protects LTP, and reduces plaques and the associated inflammation response in the brain (as assessed by measurement of activated microglia) when injected peripherally. Interestingly enough, the drug is already on the market as a treatment for type 2 diabetes (Victoza, by NovoNordisk).
This suggests that there is no need to transfer stem cells or gene vectors into the brain by intracerebroventricular injection if a growth factor analogue can be given peripherally.
Abstract at the ICAD: Liraglutide, a novel GLP-1 analogue, prevents the impairment of learning and LTP in an APP/PS-1 mouse model of Alzheimer's disease. McClean PL, Parthasarathy V, Gault VA, Hölscher C.