Skip to main content

Table 2 Animal studies using genetic manipulations of NADPH oxidases on neurodegenerative disorders

From: NADPH oxidase in brain injury and neurodegenerative disorders

Disorder

Animal model

Genetic manipulation

Manipulation Result

References

Alzheimer’s Disease

Aβ1–42 injection

p47phox −/−

↑M2 microglial phenotype (Ym1)

↓Monocyte chemoattractant (CCL2)

[205]

Tg2576

Nox2 −/−

↓Cerebrovascular dysfunction & ROS ↑Cognition

[407]

Tg2576

Aβ1–40 injection

Nox2 −/−

↓ROS & vascular dysfunction

[204]

APP-expressing neuroblastoma

Nox2 −/− macrophages (PLB-985 X-CGD)

Macrophages unable to kill APP-expressing neuroblastoma cells

[408]

Stroke

tMCAO

Nox1 −/−

↑Cortical (but not total) infarct

[59]

tMCAO

Nox1 −/−

↓Lesion, edema & BBB disruption

[409]

pMCAO

Nox1 −/−

No change in infarct size

[409]

tMCAO

Nox1 −/−

No change in infarct size or outcome

[140]

tMCAO

Nox2 −/−

No change in infarct size or outcome

[140]

tMCAO

Nox4 −/−

↓Infarct, edema & BBB disruption

↑Cognition/basal motor function

[140]

pMCAO

Nox4 −/−

↓Infarct & functional deficits

[140]

tMCAO

Nox2 −/−

↓Infarct

[160]

tMCAO

Nox2 −/−

↓Lesion & BBB disruption

[158]

Perinatal Hypoxia-Ischemia (HI)

Nox2 −/−

No change in infarct size (severe hypoxia); ↑Infarct (moderate ischemia)

[410]

tMCAO

Nox2 −/−

↓Infarct & spectrin cleavage

↑Neurological outcome

[131]

tMCAO

Nox2 −/−

↓Infarct & inflammation

[157]

tBCCAO

SAH

p47phox −/−

Nox2 −/−

↓CA1 neuronal degeneration

No change in mortality, brain water content, or intensity of oxidative stress

[411]

[172]

ICH

Nox2 −/−

↓Hematoma, edema, deficits, mortality

[171]

Traumatic Brain Injury

CCI

Nox2 −/−

↓Lesion, apoptosis & ROS

[185]

SBI

Nox2 −/−

↑Neurological outcome

[412]

Parkinson’s Disease

6-OHDA

Nox2 −/−

↑Neurological outcome & resistance to neurotoxicity

[227]

MPTP

Nox2 −/−

Neuroprotective

[218]

MPP+

Nox2 −/− neuron-glia culture

↓Dopaminergic neurodegeneration

[221]

6-OHDA

Nox2 −/−

↓Rotational behavior

[217]

Paraquat

NOX1 −/− differentiated human dopaminergic cells

↓α-synuclein expression & aggregation

[226]

Paraquat

Nox1 shRNA

↓α-synuclein expression & aggregation, ROS, dopaminergic neuronal loss

[226]

Amyotrophic Lateral Sclerosis

SOD1G93A

Nox2 −/−

↓ROS, protein carbonylation, neurodegeneration

↑Longevity

[262]

SOD1G93A

Nox1 −/−

Delayed disease progression

↑Survival

[276]

SOD1G93A

Nox2 −/−

Delayed disease progression

↓Muscle atrophy

↑Survival

[276]

SOD1G93A

Nox1 +/− or Nox2 +/−

↑Survival

[276]

Huntington’s Disease

HD140Q/140Q

Nox2 −/−

↑Neuronal viability

↓ROS

[246]

Multiple Sclerosis

MOG induced EAE

p47phox −/−

BV-2-myelin culture

↓ROS, neuroinflammation

[308]

MOG induced EAE

Nox2 −/−

↓Weight loss, microglial reactivity

↑Oligodendrocyte survival, neurological outcome

[311]

 

MOG induced EAE

p47phox −/−

↓EAE presentation

[309]

MOG induced EAE

p47phox splice mutation

Enhanced EAE presentation

[310]