Dr Elena Posse de Chaves
Office: 9-31B Medical Sciences Building (☎) 780.492.5966
Lab: 9-31 Medical Sciences Building (☎) 780.492.6006
1992: PhD (Hons) Biochemistry, Universidad Nacional de Tucumán, Argentina
1987: BSc (Pharmacy), Universidad Nacional de Tucumán, Argentina
1983: Biochemist (Professional Degree) (Hons.) Biochemistry, Universidad Nacional de Tucumán, Argentina
Teaching: PMCOL343, PMCOL344, PMCOL412, PMCOL475/575*, PMCOL508, Neuro410
Research: Role of lipids and lipoproteins in neurodegeneration in Alzheimer's disease
Our goal is to understand the molecular mechanisms of neurodegeneration in Alzheimer's disease (AD) and to identify new therapeutic targets.
AD is the most common form of age-related dementia. In 2008, 103,700 new cases of AD were diagnosed in Canada, which represents 1 case every 5 minutes. It is estimated that by 2038 the number will rise to 257,800 new cases per year (1 every 2 minutes) while the economic burden of dementia, now at $15 billion a year, will increase tenfold to $153 billion if new treatment strategies are not implemented. To accomplish this we need a better understanding of the molecular basis of the disease.
AD is characterized by the accumulation of amyloid beta (Aβ) peptide in the brain. Lipids, in particular cholesterol, are emerging as key players in AD. Cholesterol regulates Aβ production and the cholesterol transport protein apolipoprotein E (apoE4) has been long-linked to AD. The E4 isoform of apoE is one of the few risk factors consistently associated with the most common, non-familial form of AD. Moreover, controversial epidemiological studies have suggested that high cholesterol levels in mid-life are also a risk factor for AD, and that treating humans with cholesterol lowering medications might reduce the risk of developing AD or help treat it. Statins, the most prescribed medications in North America, inhibit the mevalonate/cholesterol synthesis pathway.
We have found a new link between the mevalonate pathway and Aβ-induced neurotoxicity. Our studies will help uncover the molecular mechanisms that participate in the pathophysiology of AD.
Amritraj A, Posse de Chaves EI, Hawkes C, Macdonald RG, Kar S (2012). Single-transmembrane domain IGF-II/M6P receptor: potential interaction with G protein and its association with cholesterol-rich membrane domains. Endocrinology 153(10):4784-4798. PMID: 22903618.
Posse de Chaves E (2012). Reciprocal regulation of cholesterol and beta amyloid at the subcellular level in Alzheimer's disease. Can J Physiol Pharmacol 90(6):753-64. PMID: 22626060.
Mohamed A, Saavedra L, Di PA, Sipione S and Posse de Chaves E (2012). β-amyloid inhibits protein prenylation and induces cholesterol sequestration by impairing SREBP-2 cleavage. J Neurosci 32(19):6490-6500. PMID: 22573671.
Mohamed A, Posse de Chaves E (2011). Aβ internalization by neurons and glia. Int J Alzheimers Dis 2011:127984. PMID: 21350608.
Huxtable AG, Zwicker JD, Alvares TS, Ruangkittisakul A, Fang X, Hahn LB, Posse de Chaves E, Baker GB, Ballanyi K, Funk GD (2010). Glia contribute to the purinergic modulation of inspiratory rhythm-generating networks. J Neurosci 30(11):3947-3958. PMID: 20237265.
Posse de Chaves EP, Sipione S. (2010) Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. FEBS Lett 584(9):1748-1759. PMID: 20006608.
Aglah C, Gordon T, Posse de Chaves EI (2008). cAMP promotes neurite outgrowth and extension through protein kinase A but independently of Erk activation in cultured rat motoneurons. Neuropharmacology 55(1):8-17. PMID: 18502451.
Saavedra L, Mohamed A, Ma V, Kar S, Posse de Chaves EP (2007). Internalization of β-amyloid peptide by primary neurons in the absence of apolipoprotein E. J Biol Chem 282(49):35722-35732. PMID: 17911110.
Song MS, Saavedra L, Posse de Chaves EI (2006). Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Aβ in distal axons. Neurobiol Aging. 27(9):1224-1238. PMID: 16122841.