中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (12): 2081-2082.doi: 10.4103/1673-5374.262584

• 观点:退行性病与再生 • 上一篇    下一篇

自噬缺陷和阿尔茨海默病:钙是关键吗?

  

  • 出版日期:2019-12-15 发布日期:2019-12-15

Defective autophagy and Alzheimer’s disease: is calcium the key?

Riccardo Filadi, Paola Pizzo   

  1. Department of Biomedical Sciences, University of Padua and Neuroscience Institute - Italian National Research Council (CNR), Padua, Italy
  • Online:2019-12-15 Published:2019-12-15
  • Contact: Paola Pizzo, PhD, paola.pizzo@unipd.it; Riccardo Filadi, PhD, riccardo.filadi@unipd.it.
  • Supported by:

    The work was supported by Italian Ministry of University and Scientific Research, the University of Padua (to PP); the EU Joint Programme-Neurodegenerative Disease Research (CeBioND) (to PP); UNIPD Funds for Research Equipment-2015.

摘要:

orcid: 0000-0002-5871-2620 (Riccardo Filadi)
          0000-0001-6077-3265 (Paola Pizzo)

Abstract:

Presenilins and autophagy: Presenilin 1 (PS1) and presenilin 2 (PS2) are homologous, multi-pass transmembrane proteins endowed with pleiotropic functions, ranging from the regulation of membrane trafficking to cell differentiation. Their catalytic activity within the γ-secretase complex, an aspartyl-protease responsible for the intramembrane cleavage of several different type I transmembrane proteins, has been intensively studied in the context of Alzheimer’s disease (AD). Indeed, tens of autosomal dominant mutations in the PSEN1 and PSEN2 genes (encoding PS1 and PS2, respectively) have been associated with the rare familial forms of AD (FAD). FAD-PS1/PS2 mutants are known to alter the γ-secretase-dependent cleavage of the amyloid-precursor-protein, generating amyloid-β (Aβ) peptides, whose toxicity is thought to underlie AD onset and progression. Interestingly, in the last decade, besides their γ-secretase activity, both PS1 and PS2 have been implicated in the regulation of macroautophagy (hereafter called autophagy), a key cellular pathway in which different cell material (proteins, lipids, sugars, damaged organelles) is engulfed within double-membrane vesicles (autophagosomes) and targeted to lysosomes for degradation and recycling of the molecular constituents. Considered that impairment of autophagy can promote neurodegeneration, the finding that FADlinked PSs perturb this process suggests it could be involved in AD pathogenesis.