Gamma-secretase subunits associate in intracellular membrane compartments in Arabidopsis thaliana

Alzheimer's disease (AD) is associated with deficiencies in cerebrovascular functions, e.g. reduced cerebral blood flow and capillary amyloid angiopathy, both of which are evident during the early phase of AD, thus local hypoxia/ischemia could augment the pathogenesis of AD. There is abundant literature revealing that exposures to hypoxia/ischemia increase the amyloidogenic processing of amyloid-b precursor protein (APP) leading to the accumulation of amyloid-b peptides in brain. This hypoxia-induced response has been attributed to a significant increase in the activities of b-and csecretases, whereas a-secretase activity decreases in hypoxia. Recent studies have indicated that hypoxia-inducible factor-1a (HIF-1a) stimulates the transcription of the bsecretase 1 (BACE1) gene through the hypoxia-response element in the BACE1 promoter. Moreover, HIF-1a protein can directly interact with the c-secretase complex and increase its activity in a non-transcriptional manner. Hypoxia/ischemia also trigger endoplasmic reticulum stress and impair autophagy in brain, which consequently can stimulate the expression of presenilin 1 (PS1) and activate c-secretase. Subsequently, PS1 protein can stabilize HIF-1a protein and in addition, APP intracellular domain peptide is able to induce the expression of HIF-1a. The activation of b-and c-secretases is an evolutionarily conserved hypoxia response, e.g. it is also present in zebrafish. Given that b-and c-secretases have many substrates in addition to APP, one could postulate that AD pathology is a byproduct of the rescue process mediated by these two aspartyl proteinases under hypoxic/ischemic conditions. We will review the recent evidence indicating that vascular dysfunctions can provoke AD pathology by activating b-and c-secretases.

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“…; Smolarkiewicz et al . ). For instance, there are functional γ‐secretase complexes in the social amoebae, Dictyostelium (McMains et al .…”

Section: Activation Of β‐ and γ‐Secretases Is An Evolutionarily‐consementioning

confidence: 97%

“…), and the flowering plant, Arabidopsis thaliana (Smolarkiewicz et al . ). The PS‐dependent γ‐secretase complex of Dictyostelium , containing four subunits homologs to humans, can accurately process the human APP (McMains et al .…”

Section: Activation Of β‐ and γ‐Secretases Is An Evolutionarily‐consementioning

confidence: 97%

Hypoxia/ischemia activate processing of Amyloid Precursor Protein: impact of vascular dysfunction in the pathogenesis of Alzheimer's disease

Salminen

Kauppinen

Kaarniranta

2017

Journal of Neurochemistry

158

124

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“…discoideum . Similarly, genes coding for γ-secretase subunit homologs have been recognized in plant genomes (McMains et al 2010; Smolarkiewicz 2012), but no substrate of non-metazoan origin has yet been identified.…”

Section: To Cleave or Not To Cleave? Substrate Specificity Of The γ-Smentioning

confidence: 99%

The very many faces of presenilins and the γ-secretase complex

2013

Self Cite

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Presenilin is a central, catalytic component of the γ-secretase complex which conducts intramembrane cleavage of various protein substrates. Although identified and mainly studied through its role in the development of amyloid plaques in Alzheimer disease, γ-secretase has many other important functions. The complex seems to be evolutionary conserved throughout the Metazoa, but recent findings in plants and Dictyostelium discoideum as well as in archeons suggest that its evolution and functions might be much more diversified than previously expected. In this review, a selective survey of the multitude of functions of presenilins and the γ-secretase complex is presented. Following a brief overview of γ-secretase structure, assembly and maturation, three functional aspects are analyzed: (1) the role of γ-secretase in autophagy and phagocytosis; (2) involvement of the complex in signaling related to endocytosis; and (3) control of calcium fluxes by presenilins.

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“…Research performed on A. thaliana indicates that the c-secretase complex may be involved in protein trafficking (Smolarkiewicz et al 2014).…”

Section: Rhomboids In a Thalianamentioning

confidence: 99%

Arabidopsis thaliana intramembrane proteases

et al. 2017

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Proteolysis is considered as a crucial factor determining the proper development of the plant and its efficient functioning in variable environmental conditions. The role of proteases in protein quality control and protein turnover processes is well documented. The results of studies performed in recent years reveal; however, that proteolytic enzymes also participate in signal transduction pathways by releasing membrane-anchored transcription factors in the process known as regulated intramembrane proteolysis (RIP). The first described intramembrane protease was identified in human cells in 1997. In turn, the first plant intramembrane protease was identified in 2005, in Arabidopsis thaliana. To date, most studies concerning the RIP process in plants have been performed on this model plant. The knowledge concerning the potential physiological role of RIP is very limited. However, continuously accumulating information concerning this issue indicates that RIP, like the other proteolytic mechanisms, has a significant effect on plant ontogenesis, acclimatization and fertility. The aim of this article is to gather and systemize the present knowledge concerning the intramembrane proteases in A. thaliana.

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Gamma-secretase subunits associate in intracellular membrane compartments in Arabidopsis thaliana

Cited by 21 publications

References 54 publications

Hypoxia/ischemia activate processing of Amyloid Precursor Protein: impact of vascular dysfunction in the pathogenesis of Alzheimer's disease

Hypoxia/ischemia activate processing of Amyloid Precursor Protein: impact of vascular dysfunction in the pathogenesis of Alzheimer's disease

The very many faces of presenilins and the γ-secretase complex

Arabidopsis thaliana intramembrane proteases

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