Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues?
This minireview is a brief overview examining the roles of insulin-like growth factors (IGFs) and the PI3K/Akt pathway in two apparently unconnected diseases: Alzheimer's dementia and cancer. For both, increased age is a major risk factor, and, in accord with the global rise in average life exp...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-06-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00403/full |
| _version_ | 1818251717029920768 |
|---|---|
| author | Rachel M. Barker Jeff M. P. Holly Kalina M. Biernacka Shelley J. Allen-Birt Claire M. Perks |
| author_facet | Rachel M. Barker Jeff M. P. Holly Kalina M. Biernacka Shelley J. Allen-Birt Claire M. Perks |
| author_sort | Rachel M. Barker |
| collection | DOAJ |
| description | This minireview is a brief overview examining the roles of insulin-like growth factors (IGFs) and the PI3K/Akt pathway in two apparently unconnected diseases: Alzheimer's dementia and cancer. For both, increased age is a major risk factor, and, in accord with the global rise in average life expectancy, their prevalence is also increasing. Cancer, however, involves excessive cell proliferation and metastasis, whereas Alzheimer's disease (AD) involves cell death and tissue destruction. The apparent “inverse” nature of these disease states is examined here, but also some important commonalities in terms of the PI3K/Akt pathway, glucose utilization and cell deregulation/death. The focus here is on four key molecules associated with this pathway; notably, the insulin receptor substrate 1 (IRS-1), cellular tumor antigen p53 (p53), peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) and low-density lipoprotein receptor–related protein-1 (LRP1), all previously identified as potential therapeutic targets for both diseases. The insulin-resistant state, commonly reported in AD brain, results in neuronal glucose deprivation, due to a dampening down of the PI3K/Akt pathway, including overactivity of the mammalian target of rapamycin 1 (mTORC1) complex, hyperphosphorylation of p53 and neuronal death. This contrasts with cancer, where there is overstimulation of the PI3K/Akt pathway and the suppression of mTORC1 and p53, enabling abundant energy and unrestrained cell proliferation. Although these disease states appear to be diametrically opposed, the same key molecules are controlling pathology and, with differential targeting of therapeutics, may yet provide a beneficial outcome for both. |
| first_indexed | 2024-12-12T16:12:43Z |
| format | Article |
| id | doaj.art-7a34194ef26b4c369f6d2b778a079135 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-12T16:12:43Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-7a34194ef26b4c369f6d2b778a0791352022-12-22T00:19:09ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-06-011110.3389/fendo.2020.00403549508Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues?Rachel M. Barker0Jeff M. P. Holly1Kalina M. Biernacka2Shelley J. Allen-Birt3Claire M. Perks4IGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, Southmead Hospital, University of Bristol, Bristol, United KingdomIGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, Southmead Hospital, University of Bristol, Bristol, United KingdomIGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, Southmead Hospital, University of Bristol, Bristol, United KingdomMolecular Neurobiology Group, Bristol Medical School, Translational Health Sciences, Southmead Hospital, University of Bristol, Bristol, United KingdomIGFs & Metabolic Endocrinology Group, Bristol Medical School, Translational Health Sciences, Southmead Hospital, University of Bristol, Bristol, United KingdomThis minireview is a brief overview examining the roles of insulin-like growth factors (IGFs) and the PI3K/Akt pathway in two apparently unconnected diseases: Alzheimer's dementia and cancer. For both, increased age is a major risk factor, and, in accord with the global rise in average life expectancy, their prevalence is also increasing. Cancer, however, involves excessive cell proliferation and metastasis, whereas Alzheimer's disease (AD) involves cell death and tissue destruction. The apparent “inverse” nature of these disease states is examined here, but also some important commonalities in terms of the PI3K/Akt pathway, glucose utilization and cell deregulation/death. The focus here is on four key molecules associated with this pathway; notably, the insulin receptor substrate 1 (IRS-1), cellular tumor antigen p53 (p53), peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) and low-density lipoprotein receptor–related protein-1 (LRP1), all previously identified as potential therapeutic targets for both diseases. The insulin-resistant state, commonly reported in AD brain, results in neuronal glucose deprivation, due to a dampening down of the PI3K/Akt pathway, including overactivity of the mammalian target of rapamycin 1 (mTORC1) complex, hyperphosphorylation of p53 and neuronal death. This contrasts with cancer, where there is overstimulation of the PI3K/Akt pathway and the suppression of mTORC1 and p53, enabling abundant energy and unrestrained cell proliferation. Although these disease states appear to be diametrically opposed, the same key molecules are controlling pathology and, with differential targeting of therapeutics, may yet provide a beneficial outcome for both.https://www.frontiersin.org/article/10.3389/fendo.2020.00403/fullcancerAlzheimer'sPI3K/Akt pathwayIGF-1insulinLRP1 |
| spellingShingle | Rachel M. Barker Jeff M. P. Holly Kalina M. Biernacka Shelley J. Allen-Birt Claire M. Perks Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues? Frontiers in Endocrinology cancer Alzheimer's PI3K/Akt pathway IGF-1 insulin LRP1 |
| title | Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues? |
| title_full | Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues? |
| title_fullStr | Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues? |
| title_full_unstemmed | Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues? |
| title_short | Mini Review: Opposing Pathologies in Cancer and Alzheimer's Disease: Does the PI3K/Akt Pathway Provide Clues? |
| title_sort | mini review opposing pathologies in cancer and alzheimer s disease does the pi3k akt pathway provide clues |
| topic | cancer Alzheimer's PI3K/Akt pathway IGF-1 insulin LRP1 |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00403/full |
| work_keys_str_mv | AT rachelmbarker minireviewopposingpathologiesincancerandalzheimersdiseasedoesthepi3kaktpathwayprovideclues AT jeffmpholly minireviewopposingpathologiesincancerandalzheimersdiseasedoesthepi3kaktpathwayprovideclues AT kalinambiernacka minireviewopposingpathologiesincancerandalzheimersdiseasedoesthepi3kaktpathwayprovideclues AT shelleyjallenbirt minireviewopposingpathologiesincancerandalzheimersdiseasedoesthepi3kaktpathwayprovideclues AT clairemperks minireviewopposingpathologiesincancerandalzheimersdiseasedoesthepi3kaktpathwayprovideclues |