TY - JOUR
T1 - Activation of microglial cells by PrP and β-amyloid fragments raises intracellular calcium through L-type voltage sensitive calcium channels
AU - Silei, Valerio
AU - Fabrizi, Cinzia
AU - Venturini, Giorgio
AU - Salmona, Mario
AU - Bugiani, Orso
AU - Tagliavini, Fabrizio
AU - Lauro, Giuliana Maria
PY - 1999/2/6
Y1 - 1999/2/6
N2 - The prion protein (PrP) and the amyloid β (Aβ) precursor protein (APP) are two normal proteins constitutively synthesised in human brain. An altered form of PrP accumulates in Creutzfeldt-Jakob disease, while Aβ is involved in the pathogenesis of Alzheimer's disease. Synthetic fragments of both proteins, PrP106-126 and β25-35 (β25-35), have been demonstrated to induce neurodegeneration and microglia activation. This study was undertaken to compare PrP106-126 and β25-35 capability of activating human resting microglial cells. Our results show that both peptides are able to induce microglial activation and to elicit an increase in [Ca2+](i) levels in cells loaded with calcium-green 1. Inhibitors of L-type voltage-sensitive calcium channels (verapamil, nifedipine and diltiazem) prevented the increase in [Ca2+](i) concentration as observed after treatment with PrP106-126 and β25-35, thus indicating a transmembrane calcium influx through these channels. In addition, verapamil abolished the proliferative effect of both PrP106-126 and β25-35.
AB - The prion protein (PrP) and the amyloid β (Aβ) precursor protein (APP) are two normal proteins constitutively synthesised in human brain. An altered form of PrP accumulates in Creutzfeldt-Jakob disease, while Aβ is involved in the pathogenesis of Alzheimer's disease. Synthetic fragments of both proteins, PrP106-126 and β25-35 (β25-35), have been demonstrated to induce neurodegeneration and microglia activation. This study was undertaken to compare PrP106-126 and β25-35 capability of activating human resting microglial cells. Our results show that both peptides are able to induce microglial activation and to elicit an increase in [Ca2+](i) levels in cells loaded with calcium-green 1. Inhibitors of L-type voltage-sensitive calcium channels (verapamil, nifedipine and diltiazem) prevented the increase in [Ca2+](i) concentration as observed after treatment with PrP106-126 and β25-35, thus indicating a transmembrane calcium influx through these channels. In addition, verapamil abolished the proliferative effect of both PrP106-126 and β25-35.
KW - β-amyloid
KW - Calcium channel
KW - Human microglia
KW - PrP
UR - http://www.scopus.com/inward/record.url?scp=0033528286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033528286&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(98)01272-4
DO - 10.1016/S0006-8993(98)01272-4
M3 - Article
C2 - 9914452
AN - SCOPUS:0033528286
VL - 818
SP - 168
EP - 170
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -