Limits...
Mutations in presenilin 2 and its implications in Alzheimer's disease and other dementia-associated disorders.

Cai Y, An SS, Kim S - Clin Interv Aging (2015)

Bottom Line: Only two were found in Korean populations.Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia.Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Gyeonggi-do, South Korea.

ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia. Mutations in the genes encoding presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein have been identified as the main genetic causes of familial AD. To date, more than 200 mutations have been described worldwide in PSEN1, which is highly homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We performed a systematic review of studies describing the mutations identified in PSEN2. Most PSEN2 mutations were detected in European and in African populations. Only two were found in Korean populations. Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia. Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

No MeSH data available.


Related in: MedlinePlus

The process of Aβ aggregation.Notes: Amyloid precursor protein (APP) is a transmembrane protein. APP processing includes non-amyloidogenic and amyloidogenic pathways. Non-amyloidogenic pathway (left): APP is cleaved by α-secretase in the middle of Aβ with production soluble APPα (sAPPα) and C-terminal fragment α (CTFα). Then CTFα is hydrolyzed by γ-secretase to generate APP intracellular domain (AICD). Amyloidogenic pathway (right): APP is cleaved by β-secretase resulting in N-terminal soluble APPβ (sAPPβ) leaving the C-terminal fragment β (CTFβ) which is hydrolyzed by γ-secretase to yield Aβ and AICD. Presenilin, nicastrin, anterior pharynx-defective 1 (APH-1) and presenilin enhancer 2 (PEN-2) are the parts of γ-secretase. PSEN mutation might increase γ-secretase activity to cause plaque forming.Abbreviations: AICD, APP intracellular domain; APP, amyloid precursor protein; APH-1, anterior pharynx-defective 1; CTFα, C-terminal fragment α; CTFβ, C-terminal fragment β; sAPP, soluble APP; PEN-2, presenilin enhancer 2.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4507455&req=5

f1-cia-10-1163: The process of Aβ aggregation.Notes: Amyloid precursor protein (APP) is a transmembrane protein. APP processing includes non-amyloidogenic and amyloidogenic pathways. Non-amyloidogenic pathway (left): APP is cleaved by α-secretase in the middle of Aβ with production soluble APPα (sAPPα) and C-terminal fragment α (CTFα). Then CTFα is hydrolyzed by γ-secretase to generate APP intracellular domain (AICD). Amyloidogenic pathway (right): APP is cleaved by β-secretase resulting in N-terminal soluble APPβ (sAPPβ) leaving the C-terminal fragment β (CTFβ) which is hydrolyzed by γ-secretase to yield Aβ and AICD. Presenilin, nicastrin, anterior pharynx-defective 1 (APH-1) and presenilin enhancer 2 (PEN-2) are the parts of γ-secretase. PSEN mutation might increase γ-secretase activity to cause plaque forming.Abbreviations: AICD, APP intracellular domain; APP, amyloid precursor protein; APH-1, anterior pharynx-defective 1; CTFα, C-terminal fragment α; CTFβ, C-terminal fragment β; sAPP, soluble APP; PEN-2, presenilin enhancer 2.

Mentions: Presenilin, an aspartyl protease, is a subunit of γ-secretase. γ-Secretase participates in the cleavage of APP, which can produce different lengths of β-amyloid peptide (Aβ). The Aβ42 form aggregates easier than the Aβ40 form. The accumulation of Aβ in the brain is a pathological characteristic of AD.22 The process of Aβ aggregation is shown in Figure 1. PSEN2 mutation might increase γ-secretase activity. Cell-based studies and mouse models have shown that some PSEN2 mutations cause an increased production of Aβ42, which is a major hallmark in the brains of patients with AD. Presenilin mutations are a major risk factor for AD.23 Several studies have indicated that AD-related presenilin mutations can alter intracellular calcium signaling, which leads to Aβ aggregation to form brain plaques and neuronal cell death.24,25


Mutations in presenilin 2 and its implications in Alzheimer's disease and other dementia-associated disorders.

Cai Y, An SS, Kim S - Clin Interv Aging (2015)

The process of Aβ aggregation.Notes: Amyloid precursor protein (APP) is a transmembrane protein. APP processing includes non-amyloidogenic and amyloidogenic pathways. Non-amyloidogenic pathway (left): APP is cleaved by α-secretase in the middle of Aβ with production soluble APPα (sAPPα) and C-terminal fragment α (CTFα). Then CTFα is hydrolyzed by γ-secretase to generate APP intracellular domain (AICD). Amyloidogenic pathway (right): APP is cleaved by β-secretase resulting in N-terminal soluble APPβ (sAPPβ) leaving the C-terminal fragment β (CTFβ) which is hydrolyzed by γ-secretase to yield Aβ and AICD. Presenilin, nicastrin, anterior pharynx-defective 1 (APH-1) and presenilin enhancer 2 (PEN-2) are the parts of γ-secretase. PSEN mutation might increase γ-secretase activity to cause plaque forming.Abbreviations: AICD, APP intracellular domain; APP, amyloid precursor protein; APH-1, anterior pharynx-defective 1; CTFα, C-terminal fragment α; CTFβ, C-terminal fragment β; sAPP, soluble APP; PEN-2, presenilin enhancer 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507455&req=5

f1-cia-10-1163: The process of Aβ aggregation.Notes: Amyloid precursor protein (APP) is a transmembrane protein. APP processing includes non-amyloidogenic and amyloidogenic pathways. Non-amyloidogenic pathway (left): APP is cleaved by α-secretase in the middle of Aβ with production soluble APPα (sAPPα) and C-terminal fragment α (CTFα). Then CTFα is hydrolyzed by γ-secretase to generate APP intracellular domain (AICD). Amyloidogenic pathway (right): APP is cleaved by β-secretase resulting in N-terminal soluble APPβ (sAPPβ) leaving the C-terminal fragment β (CTFβ) which is hydrolyzed by γ-secretase to yield Aβ and AICD. Presenilin, nicastrin, anterior pharynx-defective 1 (APH-1) and presenilin enhancer 2 (PEN-2) are the parts of γ-secretase. PSEN mutation might increase γ-secretase activity to cause plaque forming.Abbreviations: AICD, APP intracellular domain; APP, amyloid precursor protein; APH-1, anterior pharynx-defective 1; CTFα, C-terminal fragment α; CTFβ, C-terminal fragment β; sAPP, soluble APP; PEN-2, presenilin enhancer 2.
Mentions: Presenilin, an aspartyl protease, is a subunit of γ-secretase. γ-Secretase participates in the cleavage of APP, which can produce different lengths of β-amyloid peptide (Aβ). The Aβ42 form aggregates easier than the Aβ40 form. The accumulation of Aβ in the brain is a pathological characteristic of AD.22 The process of Aβ aggregation is shown in Figure 1. PSEN2 mutation might increase γ-secretase activity. Cell-based studies and mouse models have shown that some PSEN2 mutations cause an increased production of Aβ42, which is a major hallmark in the brains of patients with AD. Presenilin mutations are a major risk factor for AD.23 Several studies have indicated that AD-related presenilin mutations can alter intracellular calcium signaling, which leads to Aβ aggregation to form brain plaques and neuronal cell death.24,25

Bottom Line: Only two were found in Korean populations.Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia.Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Gyeonggi-do, South Korea.

ABSTRACT
Alzheimer's disease (AD) is the most common form of dementia. Mutations in the genes encoding presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein have been identified as the main genetic causes of familial AD. To date, more than 200 mutations have been described worldwide in PSEN1, which is highly homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We performed a systematic review of studies describing the mutations identified in PSEN2. Most PSEN2 mutations were detected in European and in African populations. Only two were found in Korean populations. Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson's disease with dementia. Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders.

No MeSH data available.


Related in: MedlinePlus