Intracellular Calcium Dysregulation by the Alzheimer's Disease-Linked Protein Presenilin 2

Alzheimer's disease (AD) is the most common form of dementia. Even though most AD cases are sporadic, a small percentage is familial due to autosomal dominant mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. AD mutations contribute to the gener...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-01, Vol.21 (3), p.770
Main Authors: Galla, Luisa, Redolfi, Nelly, Pozzan, Tullio, Pizzo, Paola, Greotti, Elisa
Format: Article
Language:English
Subjects:
Age
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Alzheimer's disease
Amino acids
Amyloid beta-Protein Precursor - genetics
Amyloid beta-Protein Precursor - metabolism
Amyloid precursor protein
Calcium (intracellular)
calcium dysregulation
Calcium homeostasis
Calcium ions
Calcium Signaling
Calcium signalling
Chromosomes
Dementia
Dementia disorders
Genes
genetically encoded calcium indicators
Homeostasis
Humans
Hypotheses
Musculoskeletal system
Mutation
Neurodegeneration
Pathogenesis
Peptides
Plaques
Polymorphism
Presenilin 1
Presenilin 2
Presenilin-1 - genetics
Presenilin-1 - metabolism
Presenilin-2 - genetics
Presenilin-2 - metabolism
presenilins
Proteins
Review
soce
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Description
Summary:Alzheimer's disease (AD) is the most common form of dementia. Even though most AD cases are sporadic, a small percentage is familial due to autosomal dominant mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. AD mutations contribute to the generation of toxic amyloid β (Aβ) peptides and the formation of cerebral plaques, leading to the formulation of the amyloid cascade hypothesis for AD pathogenesis. Many drugs have been developed to inhibit this pathway but all these approaches currently failed, raising the need to find additional pathogenic mechanisms. Alterations in cellular calcium (Ca ) signaling have also been reported as causative of neurodegeneration. Interestingly, Aβ peptides, mutated presenilin-1 (PS1), and presenilin-2 (PS2) variously lead to modifications in Ca homeostasis. In this contribution, we focus on PS2, summarizing how AD-linked PS2 mutants alter multiple Ca pathways and the functional consequences of this Ca dysregulation in AD pathogenesis.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21030770