Increasing evidence indicates that amyloid aggregates,including oligomers,protofibrils or fibrils,are pivotal toxins in the pathogenesis of many amyloidoses such as Alzheimer s disease(AD), Parkinson s disease,Hunting...
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Increasing evidence indicates that amyloid aggregates,including oligomers,protofibrils or fibrils,are pivotal toxins in the pathogenesis of many amyloidoses such as Alzheimer s disease(AD), Parkinson s disease,Huntington s disease,prion-related diseases,type 2 diabetes and hereditary renal *** oligomers assembled from different amyloid proteins share common structures and *** we present data indicating that two oligomer-specific single chain variable fragment(scFv) antibodies isolated from a na ve human scFv library could conformation-dependently recognize oligomers assembled fromα-synuclein,amylin,insulin,A1-40,prion peptide 106-126 and lysozyme,and fibrils from *** investigation showed that both scFv's inhibited the fibrillization ofα-synuclein,amylin, insulin,Aβ1-40 and prion peptide 106-126,and disaggregated their preformed ***,they both promoted the aggregation of ***,the two scFv antibodies could attenuate the cytotoxicity of all amyloids ***,the scFv s recognized the amyloid oligomers in all types of plaques,Lewy bodies and amylin deposits in the brain tissues of AD and PD patients and the pancreas of type 2 diabetes patients respectively,and showed that most amyloid fibril deposits were colocalized with oligomers in the *** conformation-dependent scFv antibodies may have potential application in the investigation of aggregate structures,the mechanisms of aggregation and cytotoxicity of various amyloids,and in the development of diagnostic and therapeutic reagents for many amyloidoses.
Studies have shown that women have higher risk to develop Alzheimer s disease(AD) than age-matched men due to sharp reduction of estrogen after *** studies also showed that men with AD have lower levels of brain testo...
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Studies have shown that women have higher risk to develop Alzheimer s disease(AD) than age-matched men due to sharp reduction of estrogen after *** studies also showed that men with AD have lower levels of brain testosterone compared to age-matched,non-demented men. To elucidate the mechanisms that underlie the link between sex hormones reduction and AD,we have developed an animal model,using a gene-based approach,to study the brain estrogen and testosterone effect on AD-like brain *** found that AD-like transgenic mice(APP mice) with genetic partial depletion of endogenous estrogen(APP/Ar+/- mice) showed enhanced brain amyloid production,plaque formation in females,while significant decrease in amyloid accumulation in the brain of male *** the deficiency of endogenous estrogen in APP mice cause opposite effects on brain between males and females? We performed extensive experiments and our data suggested that brain sex hormone levels and cross-talk between estrogen and testosterone might be the key players in the gender difference found in APP23/Ar+/- mice,suggesting that endogenous estrogen and testosterone(independent from estrogen) may play a significant neuroprotective role against AD,via the regulation of BACE1 and NEP activities,and may even help prevent normal age-related deficits in the brain.
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