General Information:

Id: 3,699
Diseases: Alzheimer disease - [OMIM]
Mammalia
review
Reference: Cai H et al.(2012) Metabolic dysfunction in Alzheimers disease and related neurodegenerative disorders Curr Alzheimer Res 9: 5-17 [PMID: 22329649]

Interaction Information:

Comment Uncontrolled, progressive weight loss and abnormal glucose tolerance are common metabolic dysfunctions observed in AD (Alzheimer disease), HD (Huntington disease), and PD (Parkinson disease).
Formal Description
Interaction-ID: 35731

increases_activity of

phenotype

weight loss

Comment The disease loci of AD (Alzheimer disease), HD (Huntington disease), and PD (Parkinson disease) often involve the hypothalamus, a key regulatory brain region for global energy homeostasis.
Formal Description
Interaction-ID: 35740

affects_activity of

tissue/cell line

hypothalamus

Comment The disease loci of AD (Alzheimer disease), HD (Huntington disease), and PD (Parkinson disease) often involve the hypothalamus, a key regulatory brain region for global energy homeostasis.
Formal Description
Interaction-ID: 35749

tissue/cell line

hypothalamus

affects_activity of

Comment Excess body weight during middle-age is linked to an increased risk of developing AD. Obesity (Body Mass Index - BMI greater than 30) at 40-45 years of age is associated with a 3-fold increase in the risk of developing AD, while being overweight (BMI between 25 and 30) is associated with a 2-fold increase in AD risk, compared to individuals with a normal BMI.
Formal Description
Interaction-ID: 35802

increases_activity of

at 40-45 years of age BMI>30 increased AD risk 3-fold, BMI 25-30 increased AD risk 2-fold;
Comment Rats fed a high-fat/glucose diet, to induce insulin resistance, were found to exhibit impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation in the CA1 region.
Formal Description
Interaction-ID: 35831

phenotype

insulin resistance

affects_activity of

High-fat/glucose diet was found to exhibit impaired spatial learning ability.
Comment Reducing caloric intake increases healthspan, reduces damage in the brain due to aging, and provides greater maintenance of various brain functions, potentially through hormetic mechanisms.
Formal Description
Interaction-ID: 35832

environment

calorie restriction

increases_activity of

phenotype

extended life span

Comment The Rotterdam study revealed an approximate two-fold increase in risk of developing AD in patients with diabetes (DM), compared to patients without the condition and DM requiring insulin treatment was associated with a four-fold increase in incidence of AD.
Formal Description
Interaction-ID: 35833

disease

Diabetes mellitus

increases_activity of

Comment Rats fed a high-fat/glucose diet, to induce insulin resistance, were found to exhibit impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation in the CA1 region.
Formal Description
Interaction-ID: 35834

environment

high-fat/glucose diet

increases_activity of

phenotype

insulin resistance

Comment Rats fed a high-fat/glucose diet, to induce insulin resistance, were found to exhibit impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation in the CA1 region.
Formal Description
Interaction-ID: 35835

phenotype

insulin resistance

increases_activity of

phenotype

reduced hippocampal dendritic spine density

due to a high-fat/glucose diet
Comment Rats fed a high-fat/glucose diet, to induce insulin resistance, were found to exhibit impaired spatial learning ability, reduced hippocampal dendritic spine density, and reduced long-term potentiation in the CA1 region.
Formal Description
Interaction-ID: 35836

phenotype

insulin resistance

increases_activity of

phenotype

reduced long-term potentiation

in the CA1 region; due to a high-fat/glucose diet
Comment Reducing caloric intake increases healthspan, reduces damage in the brain due to aging, and provides greater maintenance of various brain functions, potentially through hormetic mechanisms.
Formal Description
Interaction-ID: 35837

environment

calorie restriction

decreases_activity of

Comment The presence of type 2 DM and the ApoE4 allele together has also been shown to increase the risk of developing AD, to more than five-fold, compared to individuals without those two conditions.
Formal Description
Interaction-ID: 35842

gene/protein mutant

APOE (isoform E4)

increases_activity of

In the presence of type 2 DM the risk of developing AD is increased to more than five-fold, compared to individuals without those two conditions.
Comment Hyperinsulinemia is associated with a doubled risk of developing AD.
Formal Description
Interaction-ID: 35849

increases_activity of

(with a doubled risk of developing AD)
Comment Abnormal glucose homeostasis is linked to cognitive dysfunction in such that patients with either type 1 or type 2 DM display significant memory impairment and attention deficits on cognitive testing compared to control subjects.
Formal Description
Interaction-ID: 35855

increases_activity of

phenotype

cognitive impairment

in patients with either type 1 or type 2 DM display
Comment Hyperglycemia can lead to the activation of the polyol pathway, formation of advanced glycation end products, and activation of protein kinase C.
Formal Description
Interaction-ID: 35887

phenotype

hyperglycemia

increases_activity of

Comment Hyperglycemia can lead to the activation of the polyol pathway, formation of advanced glycation end products, and activation of protein kinase C.
Formal Description
Interaction-ID: 35888

phenotype

hyperglycemia

increases_quantity of

drug/chemical compound

Advanced glycation end-product

Comment Hyperglycemia can lead to the activation of the polyol pathway, formation of advanced glycation end products, and activation of protein kinase C.
Formal Description
Interaction-ID: 35890

phenotype

hyperglycemia

increases_activity of

gene/protein

Protein kinase C

Comment Administration of high amounts of glucose can induce tau cleavage and apoptosis.
Formal Description
Interaction-ID: 35891

environment

glucose supplementation

increases_processing of

gene/protein

MAPT

Comment Administration of high amounts of glucose can induce tau cleavage and apoptosis.
Formal Description
Interaction-ID: 35892

environment

glucose supplementation

increases_activity of

Comment There is a higher density of insulin receptors in the brain of AD patients compared to control subjects.
Formal Description
Interaction-ID: 35893

increases_quantity of

complex/PPI

Insulin receptor

in the brain of AD patients ; compared to control subjects
Comment Hyperinsulinemia (a marker of insulin resistance in the metabolic disease spectrum) can decrease the availability of insulin degrading enzyme (IDE), which is essential for the degradation and clearance of Abeta in the brain.
Formal Description
Interaction-ID: 35895

decreases_quantity of

gene/protein

IDE

concerning the availability of IDE
Drugbank entries Show/Hide entries for IDE
Comment Mouse models of type 1 and type 2 DM are associated with increased tau phosphorylation, which is likely secondary to glucotoxicity.
Formal Description
Interaction-ID: 35904

increases_quantity of

protein modification

MAPT-phos

in mouse; tau phosphorylation is likely secondary to glucotoxicity
Comment Mouse models of type 1 and type 2 DM are associated with increased tau phosphorylation, which is likely secondary to glucotoxicity.
Formal Description
Interaction-ID: 35908

decreases_quantity of

protein modification

MAPT-phos

in mouse; tau phosphorylation is likely secondary to glucotoxicity
Comment PPARG activation suppresses the expression of inflammatory genes, which, clinically, has been shown to ameliorate neurodegeneration.
Formal Description
Interaction-ID: 35927

gene/protein

PPARG

decreases_activity of

Drugbank entries Show/Hide entries for PPARG
Comment PPARG activation suppresses the expression of inflammatory genes, which, clinically, has been shown to ameliorate neurodegeneration.
Formal Description
Interaction-ID: 35928

gene/protein

PPARG

decreases_activity of

phenotype

neurodegeneration

PPARG activation suppresses the expression of inflammatory genes hereby ameliorating the neurodegeneration
Drugbank entries Show/Hide entries for PPARG
Comment Treatment with a PPARG agonist reduces disease-related pathology, improves learning and memory, and enhances attention in AD patients.
Formal Description
Interaction-ID: 35949

drug/chemical compound

PPARG agonist

decreases_activity of

Comment Treatment with a PPARG agonist reduces disease-related pathology, improves learning and memory, and enhances attention in AD patients.
Formal Description
Interaction-ID: 35950

drug/chemical compound

PPARG agonist

increases_activity of

in AD patients
Comment Treatment with a PPARG agonist reduces disease-related pathology, improves learning and memory, and enhances attention in AD patients.
Formal Description
Interaction-ID: 35951

drug/chemical compound

PPARG agonist

increases_activity of

process

attention

in AD patients
Comment The cyclooxygenase inhibitor Ibuprofen (iso-butyl-propanoic-phenolic acid), which can activate PPARG, has been demonstrated to significantly reduce amyloid pathology and reduce microglial-mediated inflammation in a mouse model of AD, potentially via PPARG signaling.
Formal Description
Interaction-ID: 35952

drug/chemical compound

Ibuprofen

increases_activity of

gene/protein

PPARG

in a mouse model of AD
Drugbank entries Show/Hide entries for Ibuprofen or PPARG
Comment The cyclooxygenase inhibitor Ibuprofen (iso-butyl-propanoic-phenolic acid), which can activate PPARG, has been demonstrated to significantly reduce amyloid pathology and reduce microglial-mediated inflammation in a mouse model of AD, potentially via PPARG signaling.
Formal Description
Interaction-ID: 35954

drug/chemical compound

Ibuprofen

decreases_activity of

in a mouse model of AD
Drugbank entries Show/Hide entries for Ibuprofen
Comment The cyclooxygenase inhibitor Ibuprofen (iso-butyl-propanoic-phenolic acid), which can activate PPARG, has been demonstrated to significantly reduce amyloid pathology and reduce microglial-mediated inflammation in a mouse model of AD, potentially via PPARG signaling.
Formal Description
Interaction-ID: 35957

drug/chemical compound

Ibuprofen

decreases_activity of

phenotype

beta-amyloid pathology

in a mouse model of AD
Drugbank entries Show/Hide entries for Ibuprofen
Comment PPARG agonists have been shown to reduce Abeta plaque burden and Abeta42 (a specifically toxic form of Abeta) levels in the brain by approximately 20-25%, restore insulin responsiveness and lower glucocorticoid levels in mouse models of AD.
Formal Description
Interaction-ID: 35961

drug/chemical compound

PPARG agonist

decreases_quantity of

Comment PPARG agonists have been shown to reduce Abeta plaque burden and Abeta42 (a specifically toxic form of Abeta) levels in the brain by approximately 20-25%, restore insulin responsiveness and lower glucocorticoid levels in mouse models of AD.
Formal Description
Interaction-ID: 35963

drug/chemical compound

PPARG agonist

decreases_quantity of

Comment PPARG agonists have been shown to reduce Abeta plaque burden and Abeta42 (a specifically toxic form of Abeta) levels in the brain by approximately 20-25%, restore insulin responsiveness and lower glucocorticoid levels in mouse models of AD.
Formal Description
Interaction-ID: 35967

drug/chemical compound

PPARG agonist

increases_activity of

Comment PPARG agonists have been shown to reduce Abeta plaque burden and Abeta42 (a specifically toxic form of Abeta) levels in the brain by approximately 20-25%, restore insulin responsiveness and lower glucocorticoid levels in mouse models of AD.
Formal Description
Interaction-ID: 35968

drug/chemical compound

PPARG agonist

decreases_activity of

Comment PPARG also transcriptionally induces IDE expression, which could explain the effectiveness of PPARG agonists in treating both type 2 DM and AD.
Formal Description
Interaction-ID: 35971

gene/protein

PPARG

increases_expression of

gene/protein

IDE

Drugbank entries Show/Hide entries for PPARG or IDE
Comment PPARD, which is expressed at higher levels in the brain than PPARG, also plays a role in regulating lipid and glucose metabolism.
Formal Description
Interaction-ID: 35975

gene/protein

PPARD

affects_activity of

Drugbank entries Show/Hide entries for PPARD
Comment PPARD, which is expressed at higher levels in the brain than PPARG, also plays a role in regulating lipid and glucose metabolism.
Formal Description
Interaction-ID: 35983

gene/protein

PPARD

affects_activity of

Drugbank entries Show/Hide entries for PPARD
Comment PPARD, which is expressed at higher levels in the brain than PPARG, also plays a role in regulating lipid and glucose metabolism.
Formal Description
Interaction-ID: 35984

gene/protein

PPARD

is_expressed_in

tissue/cell line

brain

PPARD is expressed at higher levels in the brain than PPARG.
Drugbank entries Show/Hide entries for PPARD
Comment The PPARD agonist, GW742, reduced amyloid burden, an effect thought to be mediated by alterations in amyloid clearance.
Formal Description
Interaction-ID: 36001

drug/chemical compound

GW742

decreases_quantity of

Comment AD patients with significant weight loss display lower plasma leptin levels than weightstable AD patients, and disruption of homeostasis between leptin and cortisol is also observed in some AD patients.
Formal Description
Interaction-ID: 36007

cooccurs with

in AD patients
Comment AD patients with significant weight loss display lower plasma leptin levels than weightstable AD patients, and disruption of homeostasis between leptin and cortisol is also observed in some AD patients.
Formal Description
Interaction-ID: 36024

affects_activity of

process

homeostasis between leptin and cortisol

in some AD patients
Comment Lower plasma leptin levels were associated with a higher risk of incident AD. Leptin may be directly involved in the development of AD symptoms by exerting effects on the brain, as high expression of leptin receptors are found in the hippocampus, suggesting that leptin plays a role in controlling learning and memory. Leptin - besides its role in energy regulation - may directly regulate the behavioral and pathological progression of AD.
Formal Description
Interaction-ID: 36037

increases_activity of

Comment Lower plasma leptin levels were associated with a higher risk of incident AD. Leptin may be directly involved in the development of AD symptoms by exerting effects on the brain, as high expression of leptin receptors are found in the hippocampus, suggesting that leptin plays a role in controlling learning and memory.
Formal Description
Interaction-ID: 36038

gene/protein

LEPR

is_expressed_in

tissue/cell line

hippocampus

Comment Leptin treatment can promote Abeta clearance by reducing beta-secretase activity and increasing ApoE-dependent Abeta uptake, and it also improves memory performance in AD animal models.
Formal Description
Interaction-ID: 36039

gene/protein

LEP

affects_quantity of

gene/protein

Amyloid beta peptide

in AD animal models
Comment Leptin treatment can promote Abeta clearance by reducing beta-secretase activity and increasing ApoE-dependent Abeta uptake, and it also improves memory performance in AD animal models.
Formal Description
Interaction-ID: 36043

gene/protein

LEP

decreases_activity of

gene/protein

BACE1

in AD animal models
Drugbank entries Show/Hide entries for BACE1
Comment Leptin treatment can promote Abeta clearance by reducing beta-secretase activity and increasing ApoE-dependent Abeta uptake, and it also improves memory performance in AD animal models.
Formal Description
Interaction-ID: 36044

gene/protein

LEP

affects_activity of

gene/protein

APOE

in AD animal models
Drugbank entries Show/Hide entries for APOE
Comment Leptin treatment can promote Abeta clearance by reducing beta-secretase activity and increasing ApoE-dependent Abeta uptake, and it also improves memory performance in AD animal models, e.g. Leptin administration improves memory in SAMP-8 mice, an accelerated senescence rodent model that develops amyloid plaques.
Formal Description
Interaction-ID: 36045

gene/protein

LEP

increases_activity of

in AD animal models
Comment Leptin can also reduce tau phosphorylation through inactivation of GSK3B.
Formal Description
Interaction-ID: 36085

gene/protein

LEP

decreases_phosphorylation of

protein modification

MAPT-phos

Comment Leptin can also reduce tau phosphorylation through inactivation of GSK3B.
Formal Description
Interaction-ID: 36086

gene/protein

LEP

decreases_activity of

gene/protein

GSK3B

Drugbank entries Show/Hide entries for GSK3B
Comment Direct administration of leptin into the brain has been observed to facilitate hippocampal long-term potentiation.
Formal Description
Interaction-ID: 36088

gene/protein

LEP

increases_activity of

in hippocampus; after direct administration of leptin into the brain
Comment Circulating ghrelin binds to neurons of the hippocampal formation, promoting dendritic spine formation and generation of long-term potentiation (LTP).
Formal Description
Interaction-ID: 36093

gene/protein

Ghrelin

is localized in

tissue/cell line

brain

bound to neurons of the hippocampal formation
Comment Circulating ghrelin binds to neurons of the hippocampal formation, promoting dendritic spine formation and generation of long-term potentiation (LTP).
Formal Description
Interaction-ID: 36094

gene/protein

Ghrelin

increases_activity of

Comment Circulating ghrelin binds to neurons of the hippocampal formation, promoting dendritic spine formation and generation of long-term potentiation (LTP).
Formal Description
Interaction-ID: 36095

gene/protein

Ghrelin

increases_activity of

Comment Targeted disruption of ghrelin signaling resulted in a decreased number of spine synapses in the stratum radiatum and impaired performance in behavioral memory testing, both of which were rapidly restored by ghrelin administration.
Formal Description
Interaction-ID: 36098

gene/protein

Ghrelin

affects_activity of

Comment Ghrelin levels in the brain are altered in some Alzheimer's patients, suggesting that changes to the ghrelin signaling system may indeed contribute to AD pathophysiology.
Formal Description
Interaction-ID: 36099

increases_activity of

Comment One clinical study demonstrated that some AD patients have elevated levels of adiponectin in both plasma and cerebrospinal fluid (CSF), suggesting that it may play a role in mediating AD progression, possibly through its effects on peripheral or brain metabolism.
Formal Description
Interaction-ID: 36117

increases_activity of

in both plasma and cerebrospinal fluid; in some AD patients
Comment Elevated interleukin-6 has been detected in the brains of some AD patients, and that treatment with adiponectin can reduce the secretion of the centrally active interleukin-6 from brain endothelial cells.
Formal Description
Interaction-ID: 36118

increases_activity of

in AD brain
Comment Elevated interleukin-6 has been detected in the brains of some AD patients, and that treatment with adiponectin can reduce the secretion of the centrally active interleukin-6 from brain endothelial cells.
Formal Description
Interaction-ID: 36148

gene/protein

ADIPOQ

decreases_activity of

from brain endothelial cells; in AD patients
Comment GLP-1 and exendin-4, a natural and stable long-acting analogue of GLP-1, possess neurotrophic properties and protect neurons against Abeta and oxidative insults.
Formal Description
Interaction-ID: 36184

gene/protein

GCG

affects_activity of

gene/protein

Amyloid beta peptide

Comment GLP-1 and exendin-4, a natural and stable long-acting analogue of GLP-1, possess neurotrophic properties and protect neurons against Abeta and oxidative insults.
Formal Description
Interaction-ID: 36185

drug/chemical compound

Exendin-4

affects_activity of

gene/protein

Amyloid beta peptide

Comment GLP-1 and exendin-4, a natural and stable long-acting analogue of GLP-1, possess neurotrophic properties and protect neurons against Abeta and oxidative insults.
Formal Description
Interaction-ID: 36186

gene/protein

GLP1

decreases_activity of

phenotype

oxidative insult

Comment GLP-1 and exendin-4, a natural and stable long-acting analogue of GLP-1, possess neurotrophic properties and protect neurons against Abeta and oxidative insults.
Formal Description
Interaction-ID: 36187

drug/chemical compound

Exendin-4

decreases_activity of

phenotype

oxidative insult

Comment GLP-1 can reduce amyloid-beta peptide levels in vivo and decreases levels of amyloid precursor protein in cultured neuronal cells, implying that GLP-1 could be effective at reducing plaque load in AD.
Formal Description
Interaction-ID: 36191

gene/protein

GLP1

decreases_quantity of

gene/protein

APP

in cultured neuronal cells
Drugbank entries Show/Hide entries for APP
Comment GLP-1 receptor agonists protect neurons against Abeta and glutamate-induced apoptosis in cells and attenuate cholinergic neuron atrophy in the basal forebrain of the rat following an excitotoxic lesion.
Formal Description
Interaction-ID: 36341

drug/chemical compound

GLP1R agonist

decreases_activity of

gene/protein

Amyloid beta peptide

thereby protecting neurons
Comment GLP-1 receptor agonists protect neurons against Abeta and glutamate-induced apoptosis in cells and attenuate cholinergic neuron atrophy in the basal forebrain of the rat following an excitotoxic lesion.
Formal Description
Interaction-ID: 36342

drug/chemical compound

GLP1R agonist

increases_activity of

process

neuroprotection

Comment GLP-1 receptor agonists protect neurons against Abeta and glutamate-induced apoptosis in cells and attenuate cholinergic neuron atrophy in the basal forebrain of the rat following an excitotoxic lesion.
Formal Description
Interaction-ID: 36343

drug/chemical compound

GLP1R agonist

decreases_activity of

glutamate-induced
Comment GLP-1 receptor agonists protect neurons against Abeta and glutamate-induced apoptosis in cells and attenuate cholinergic neuron atrophy in the basal forebrain of the rat following an excitotoxic lesion.
Formal Description
Interaction-ID: 36344

drug/chemical compound

GLP1R agonist

decreases_activity of

phenotype

cholinergic neuron atrophy

in the basal forebrain; of rats
Comment Attenuation of the activity levels of dipeptidyl peptidase 4 (DPP-4, cleaves and inactivates GLP-1), can stabilize the plasma levels of the bioactive GLP-1.
Formal Description
Interaction-ID: 36345

gene/protein

DPP4

increases_processing of

gene/protein

GLP1

Drugbank entries Show/Hide entries for DPP4
Comment Attenuation of the activity levels of dipeptidyl peptidase 4 (DPP-4, cleaves and inactivates GLP-1), can stabilize the plasma levels of the bioactive GLP-1.
Formal Description
Interaction-ID: 36346

gene/protein

DPP4

decreases_activity of

gene/protein

GLP1

Drugbank entries Show/Hide entries for DPP4
Comment GCG is cleaved into 8 chains. One chain is GLP1.
Formal Description
Interaction-ID: 36347

gene/protein

GCG

affects_quantity of

gene/protein

GLP1

Comment Sitagliptin, a DPP-4 inhibitor, could significantly delay some forms of AD pathology, including amyloid deposition, when administrated early in the disease course in a mouse model of AD.
Formal Description
Interaction-ID: 36348

drug/chemical compound

Sitagliptin

decreases_activity of

gene/protein

DPP4

Drugbank entries Show/Hide entries for Sitagliptin or DPP4
Comment Sitagliptin, a DPP-4 inhibitor, could significantly delay some forms of AD pathology, including amyloid deposition, when administrated early in the disease course in a mouse model of AD.
Formal Description
Interaction-ID: 36349

drug/chemical compound

Sitagliptin

decreases_activity of

in a mouse model of AD
Drugbank entries Show/Hide entries for Sitagliptin
Comment Sitagliptin, a DPP-4 inhibitor, could significantly delay some forms of AD pathology, including amyloid deposition, when administrated early in the disease course in a mouse model of AD.
Formal Description
Interaction-ID: 36350

drug/chemical compound

Sitagliptin

decreases_quantity of

in a mouse model of AD when administrated early in the disease course
Drugbank entries Show/Hide entries for Sitagliptin
Comment BDNF signaling has been shown to be impaired in AD, which could be relevant considering the neurological and metabolic abnormalities noted in AD.
Formal Description
Interaction-ID: 36351

decreases_activity of

gene/protein

BDNF

Comment Studies have demonstrated low brain BDNF mRNA expression in patients with AD, including the hippocampus, neocortex and in the nucleus basalis of Meynert.
Formal Description
Interaction-ID: 36354

decreases_expression of

gene/protein

BDNF

in patients with AD, including the hippocampus, neocortex and in the nucleus basalis of Meynert
Comment Sorting protein-related receptor with A-type repeats (SORLA) regulates APP intracellular trafficking and processing into Abeta, and when overexpressed, can reduce amyloid plaque formation.
Formal Description
Interaction-ID: 36355

gene/protein

SORL1

affects transport of

gene/protein

APP

(intracellular trafficking)
Drugbank entries Show/Hide entries for APP
Comment Sorting protein-related receptor with A-type repeats (SORLA) regulates APP intracellular trafficking and processing into Abeta, and when overexpressed, can reduce amyloid plaque formation.
Formal Description
Interaction-ID: 36357

gene/protein

SORL1

affects_processing of

gene/protein

APP

into Abeta
Drugbank entries Show/Hide entries for APP
Comment Sorting protein-related receptor with A-type repeats (SORLA) regulates APP intracellular trafficking and processing into Abeta, and when overexpressed, can reduce amyloid plaque formation.
Formal Description
Interaction-ID: 36358

gene/protein

SORL1

decreases_quantity of

if overexpressed
Comment BDNF was found to be a major inducer of SORLA gene transcription through the extracellular regulated kinase (ERK) pathway. It is possible that a gradual decrease in BDNF levels may contribute to the increase in the risk of developing AD with advancing age.
Formal Description
Interaction-ID: 36360

gene/protein

BDNF

increases_expression of

gene/protein

SORL1

via extracellular regulated kinase (ERK) pathway