beta amyloid-induced disruption of ionic balance: studies on the isolated frog labyrinth.
The beta-amyloid peptide (A beta) is a key player in the pathogenesis of Alzheimer's disease. Although its mechanisms of action are not fully elucidated, a disruption of ionic homeostasis has been suggested, and A beta aggregation in fibrils seems correlated to its toxic potential. In the present work, we studied the effects of different A beta fragments on the activity of frog ampullar nerve fibers. Our results show that A beta fragments are able to reduce ampullar nerve responses, with a potency correlated to their fibrillogenic capability. This study may have clinical implications, since vestibular problems are often reported in Alzheimer patients, and provide a model for the dissection of A beta effects in a simple multicomponent system.
Botta
L
L
Department of Cell and Molecular Physiological and Pharmacological Sciences, Via Forlanini 6, University of Pavia, 27100 Pavia, Italy.
Valli
P
P
Asti
A
A
Perin
P
P
Zucca
G
G
Racchi
M
M
Govoni
S
S
Pascale
A
A
D000200:Action Potentials / Q000187:drug effects; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D011893:Rana esculenta; D012665:Semicircular Canals / Q000502:physiology*; D014725:Vestibular Nerve / Q000502:physiology; D014722:Vestibule, Labyrinth / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000187:drug effects* / Q000502:physiology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)