General Information:

Id: 667
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Celsi F et al.(2009) Mitochondria, calcium and cell death: a deadly triad in neurodegeneration Biochim. Biophys. Acta 1787: 335-344 [PMID: 19268425]

Interaction Information:

Comment An alteration in intracellular Ca2+ homeostasis contributes to the development of FAD (familial form of Alzheimer Disease), and more in general to the pathogenesis of AD.
Formal Description
Interaction-ID: 3558

increases_activity of

Comment Presenilin mutations were shown to alter the expression, or the sensitivity, of ER Ca2+ release channels (RyR and IP3R) in different cell models and in neurons from Tg AD mice, leading to the Ca2+ overload hypothesis.
Formal Description
Interaction-ID: 3569

gene/protein mutant

PSEN1-mut

affects_activity of

complex/PPI

Calcium-release channel

in endoplasmic reticulum; ''Ca2+ overload'' hypothesis
Comment Intra-mitochondrial Abeta was demonstrated to directly interact with cyclophilin D (CypD), the PTP (permeability transition pore) component that binds CsA and renders the channel more sensitive to Ca2+, making AD mitochondria more sensitive to PTP opening.
Formal Description
Interaction-ID: 3585

gene/protein

Amyloid beta peptide

interacts (colocalizes) with

gene/protein

PPIF

in mitochondrion
Drugbank entries Show/Hide entries for PPIF
Comment APP can interact with the mitochondrial TIM/TOM protein import complex. The presence of an acidic domain within APP sequence may be responsible for an incomplete mitochondrial translocation that, in turn, inhibited the entry of nuclear-encoded mitochondrial proteins.
Formal Description
Interaction-ID: 3599

gene/protein

APP

interacts (colocalizes) with

complex/PPI

TOM complex, mitochondrial

in mitochondrion
Drugbank entries Show/Hide entries for APP
Comment APP can interact with the mitochondrial TIM/TOM protein import complex. The presence of an acidic domain within APP sequence may be responsible for an incomplete mitochondrial translocation that, in turn, inhibited the entry of nuclear-encoded mitochondrial proteins.
Formal Description
Interaction-ID: 3601

gene/protein

APP

interacts (colocalizes) with

complex/PPI

TIM complex, mitochondrial

in mitochondrion
Drugbank entries Show/Hide entries for APP
Comment Electron microscopy analysis of mitochondria in various regions of AD brain revealed significant morphological organelle alterations, such as reduced size of mitochondrial cristae.
Formal Description
Interaction-ID: 3637

decreases_quantity of

cellular component

mitochondrial crista

Comment Electron microscopy analysis of mitochondria in various regions of AD brain revealed significant morphological organelle alterations, such as reduced size of mitochondrial cristae.
Formal Description
Interaction-ID: 3639

affects_activity of

Comment Presenilin mutations were shown to alter the expression, or the sensitivity, of ER Ca2+ release channels (RyR and IP3R) in different cell models and in neurons from Tg AD mice, leading to the Ca2+ overload hypothesis.
Formal Description
Interaction-ID: 4527

gene/protein mutant

PSEN2-mut

affects_activity of

complex/PPI

Calcium-release channel

in endoplasmic reticulum; ''Ca2+ overload'' hypothesis