Accelerated pre-senile systemic amyloidosis in PACAP knockout mice - a protective role of PACAP in age-related degenerative processes

The Journal of Pathology
Dora ReglodiA Bardosi

Abstract

Dysregulation of neuropeptides may play an important role in aging-induced impairments. Among them, pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue-damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life and the well-known general cytoprotective effects of PACAP lead to age-related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP. Using young and aging CD1 PACAP knockout (KO) and wild type (WT) mice, we demonstrated pre-senile amyloidosis in young PACAP KO animals and showed that senile amyloidosis appeared accelerated, more generalized, more severe, and affected more individuals. Histopathology showed age-related systemic amyloidosis with mainly kidney, spleen, liver, skin, thyroid, intestinal, tracheal, and esophageal involvement. Mass spectrometry-based proteomic analysis, reconfirmed with immunohistochemistry, revealed that apolipoprotein-AIV was the main amyloid protein in the deposits together with several accompanying proteins. Although the local amyloidogenic protein expressi...Continue Reading

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Citations

May 17, 2019·Expert Review of Proteomics·Laura GiustiAntonio Lucacchini
Oct 24, 2018·Aging·Michael J ThompsonMatteo Pellegrini
Sep 20, 2019·Translational Psychiatry·Shlomo SragovichIllana Gozes
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Jan 21, 2021·International Journal of Molecular Sciences·Etelka PöstyéniRóbert Gábriel
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Aug 10, 2021·Frontiers in Neuroscience·Yukio AgoJames A Waschek
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Nov 18, 2020·Current Protein & Peptide Science·Nhu Q VuLingjun Li
Apr 26, 2021·Journal of Molecular Neuroscience : MN·Timea KvarikTamas Atlasz

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Methods Mentioned

BETA
PCR
Profiler
biopsies
genotyping

Software Mentioned

FlexImaging
SCiLS Lab

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