Limits...
Role of apolipoprotein E in neurodegenerative diseases.

Giau VV, Bagyinszky E, An SS, Kim SY - Neuropsychiatr Dis Treat (2015)

Bottom Line: APOE-dependent alterations of the endocytic pathway can affect different functions.This review will summarize the updated research progress on APOE functions and its role in Alzheimer's disease, Parkinson's disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke.Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans.

View Article: PubMed Central - PubMed

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

ABSTRACT
Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. APOE-dependent alterations of the endocytic pathway can affect different functions. APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. Several APOE isoforms with major structural differences were discovered and shown to influence the brain lipid transport, glucose metabolism, neuronal signaling, neuroinflammation, and mitochondrial function. This review will summarize the updated research progress on APOE functions and its role in Alzheimer's disease, Parkinson's disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke. Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans.

No MeSH data available.


Related in: MedlinePlus

APOE formation and its role in redistribution of lipids to the cells of CNS: the neuropathological effects of the neurotoxic APOE fragments.Notes: ① APOE mainly produced by astrocytes, either pericytes, microglia, or under certain pathological conditions (stressors, injurious agents, etc). ② The role of APOE in the production of Aβ in association with APP. ③ The result of APOE fragmentation is associated with cytoskeletal disruption and mitochondrial dysfunction. ④ APOE isoform-specifically and Aβ-induced lysosomal leakage and apoptosis.Abbreviations: Aβ, amyloid-β; APOE, apolipoprotein E; APP, amyloid precursor protein; LRP, lipoprotein receptor-related protein 1; CNS, central nervous system.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4509527&req=5

f1-ndt-11-1723: APOE formation and its role in redistribution of lipids to the cells of CNS: the neuropathological effects of the neurotoxic APOE fragments.Notes: ① APOE mainly produced by astrocytes, either pericytes, microglia, or under certain pathological conditions (stressors, injurious agents, etc). ② The role of APOE in the production of Aβ in association with APP. ③ The result of APOE fragmentation is associated with cytoskeletal disruption and mitochondrial dysfunction. ④ APOE isoform-specifically and Aβ-induced lysosomal leakage and apoptosis.Abbreviations: Aβ, amyloid-β; APOE, apolipoprotein E; APP, amyloid precursor protein; LRP, lipoprotein receptor-related protein 1; CNS, central nervous system.

Mentions: In humans, there are three major isoforms of APOE, which are associated with lipoproteins in the plasma, and absorption of APOE-containing lipoprotein complexes by LDL receptors through lipid metabolism has important implications in diseases (Figure 1).5,6 Clinical studies have shown that APOE4 is associated with higher plasma total cholesterol and LDL, followed by APOE3 and APOE2.7,8 This is largely attributed to APOE4 preferentially binding to VLDL and APOE3 to HDL.9


Role of apolipoprotein E in neurodegenerative diseases.

Giau VV, Bagyinszky E, An SS, Kim SY - Neuropsychiatr Dis Treat (2015)

APOE formation and its role in redistribution of lipids to the cells of CNS: the neuropathological effects of the neurotoxic APOE fragments.Notes: ① APOE mainly produced by astrocytes, either pericytes, microglia, or under certain pathological conditions (stressors, injurious agents, etc). ② The role of APOE in the production of Aβ in association with APP. ③ The result of APOE fragmentation is associated with cytoskeletal disruption and mitochondrial dysfunction. ④ APOE isoform-specifically and Aβ-induced lysosomal leakage and apoptosis.Abbreviations: Aβ, amyloid-β; APOE, apolipoprotein E; APP, amyloid precursor protein; LRP, lipoprotein receptor-related protein 1; CNS, central nervous system.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4509527&req=5

f1-ndt-11-1723: APOE formation and its role in redistribution of lipids to the cells of CNS: the neuropathological effects of the neurotoxic APOE fragments.Notes: ① APOE mainly produced by astrocytes, either pericytes, microglia, or under certain pathological conditions (stressors, injurious agents, etc). ② The role of APOE in the production of Aβ in association with APP. ③ The result of APOE fragmentation is associated with cytoskeletal disruption and mitochondrial dysfunction. ④ APOE isoform-specifically and Aβ-induced lysosomal leakage and apoptosis.Abbreviations: Aβ, amyloid-β; APOE, apolipoprotein E; APP, amyloid precursor protein; LRP, lipoprotein receptor-related protein 1; CNS, central nervous system.
Mentions: In humans, there are three major isoforms of APOE, which are associated with lipoproteins in the plasma, and absorption of APOE-containing lipoprotein complexes by LDL receptors through lipid metabolism has important implications in diseases (Figure 1).5,6 Clinical studies have shown that APOE4 is associated with higher plasma total cholesterol and LDL, followed by APOE3 and APOE2.7,8 This is largely attributed to APOE4 preferentially binding to VLDL and APOE3 to HDL.9

Bottom Line: APOE-dependent alterations of the endocytic pathway can affect different functions.This review will summarize the updated research progress on APOE functions and its role in Alzheimer's disease, Parkinson's disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke.Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans.

View Article: PubMed Central - PubMed

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

ABSTRACT
Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. APOE-dependent alterations of the endocytic pathway can affect different functions. APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. Several APOE isoforms with major structural differences were discovered and shown to influence the brain lipid transport, glucose metabolism, neuronal signaling, neuroinflammation, and mitochondrial function. This review will summarize the updated research progress on APOE functions and its role in Alzheimer's disease, Parkinson's disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke. Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans.

No MeSH data available.


Related in: MedlinePlus