Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease
Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterize...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/8/1983 |
| _version_ | 1797524291418324992 |
|---|---|
| author | Erika Kropf Margaret Fahnestock |
| author_facet | Erika Kropf Margaret Fahnestock |
| author_sort | Erika Kropf |
| collection | DOAJ |
| description | Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75<sup>NTR</sup>. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function. |
| first_indexed | 2024-03-10T08:55:15Z |
| format | Article |
| id | doaj.art-1d96dd72c02543f294ef4e70fab9425f |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T08:55:15Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1d96dd72c02543f294ef4e70fab9425f2023-11-22T07:10:04ZengMDPI AGCells2073-44092021-08-01108198310.3390/cells10081983Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s DiseaseErika Kropf0Margaret Fahnestock1Graduate Program in Neuroscience, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, Hamilton, ON L8S 4K1, CanadaNerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75<sup>NTR</sup>. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.https://www.mdpi.com/2073-4409/10/8/1983oxidative stressnitrative stressneurotrophinp75<sup>NTR</sup>basal forebrainretrograde transport |
| spellingShingle | Erika Kropf Margaret Fahnestock Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease Cells oxidative stress nitrative stress neurotrophin p75<sup>NTR</sup> basal forebrain retrograde transport |
| title | Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease |
| title_full | Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease |
| title_fullStr | Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease |
| title_full_unstemmed | Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease |
| title_short | Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease |
| title_sort | effects of reactive oxygen and nitrogen species on trka expression and signalling implications for prongf in aging and alzheimer s disease |
| topic | oxidative stress nitrative stress neurotrophin p75<sup>NTR</sup> basal forebrain retrograde transport |
| url | https://www.mdpi.com/2073-4409/10/8/1983 |
| work_keys_str_mv | AT erikakropf effectsofreactiveoxygenandnitrogenspeciesontrkaexpressionandsignallingimplicationsforprongfinagingandalzheimersdisease AT margaretfahnestock effectsofreactiveoxygenandnitrogenspeciesontrkaexpressionandsignallingimplicationsforprongfinagingandalzheimersdisease |