Looked in Nature Medicine for that abstract, but all I could find on line was this interesting and somewhat related article (particularly as we discussed beta blockers here recently):
Article
Nature Medicine - 12, 1390 - 1396 (2006)
Published online: 19 November 2006; | doi:10.1038/nm1485
Activation of bold beta2-adrenergic receptor stimulates big gamma-secretase activity and accelerates amyloid plaque formation
Yanxiang Ni1, 3, Xiaohui Zhao1, 3, Guobin Bao1, Lin Zou1, Lin Teng1, Zhu Wang1, Min Song2, Jiaxiang Xiong2, Yun Bai2 & Gang Pei1
1 Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Graduate School of the Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
2 Department of Medical Genetics, Third Military Medical University, 30 Gao Tan Yan, Chongqing 400038, China.
3 These authors contributed equally to this work.
Correspondence should be addressed to Gang Pei gpei@sibs.ac.cn
Amyloid plaque is the hallmark and primary cause of Alzheimer disease. Mutations of presenilin-1, the bold gamma-secretase catalytic subunit, can affect amyloid-beta (Abeta) production and Alzheimer disease pathogenesis. However, it is largely unknown whether and how bold gamma-secretase activity and amyloid plaque formation are regulated by environmental factors such as stress, which is mediated by receptors including beta2-adrenergic receptor (beta2-AR). Here we report that activation of beta2-AR enhanced bold gamma-secretase activity and thus Abeta production. This enhancement involved the association of beta2-AR with presenilin-1 and required agonist-induced endocytosis of beta2-AR and subsequent trafficking of bold gamma-secretase to late endosomes and lysosomes, where Abeta production was elevated. Similar effects were observed after activation of delta-opioid receptor. Furthermore, chronic treatment with beta2-AR agonists increased cerebral amyloid plaques in an Alzheimer disease mouse model. Thus, beta2-AR activation can stimulate bold gamma-secretase activity and amyloid plaque formation, which suggests that abnormal activation of beta2-AR might contribute to Abeta accumulation in Alzheimer disease pathogenesis.
Different beta blockers have different degrees of selectivity for beta1 vs beta2. Usually beta 1 selectivity was viewed as an advantage as they were less likely to induce asthma. Propranolol (to my recollection) is non-selective between beta 1 and beta 2.
Peter |
