The Old Second Messenger CAMP Teams Up with Novel Cell Death Mechanisms: Potential Translational Therapeutical Benefit for Alzheimer's Disease and Parkinson's Disease

Overview

Journal Front Physiol

Date 2023 Jul 5

PMID 37405135

Authors

Tong Zhang

Minh D A Luu

Amalia M Dolga

Ulrich L M Eisel

Martina Schmidt

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most prevalent neurodegenerative disorders severely impacting life expectancy and quality of life of millions of people worldwide. AD and PD exhibit both a very distinct pathophysiological disease pattern. Intriguingly, recent researches, however, implicate that overlapping mechanisms may underlie AD and PD. In AD and PD, novel cell death mechanisms, encompassing parthanatos, netosis, lysosome-dependent cell death, senescence and ferroptosis, apparently rely on the production of reactive oxygen species, and seem to be modulated by the well-known, "old" second messenger cAMP. Signaling of cAMP via PKA and Epac promotes parthanatos and induces lysosomal cell death, while signaling of cAMP via PKA inhibits netosis and cellular senescence. Additionally, PKA protects against ferroptosis, whereas Epac1 promotes ferroptosis. Here we review the most recent insights into the overlapping mechanisms between AD and PD, with a special focus on cAMP signaling and the pharmacology of cAMP signaling pathways.

Citing Articles

Disulfidptosis: A new type of cell death.

Xiao F, Li H, Yang B, Che H, Xu F, Li G Apoptosis. 2024; 29(9-10):1309-1329.

PMID: 38886311 PMC: 11416406. DOI: 10.1007/s10495-024-01989-8.

Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia-reperfusion rats by activating Prkaca-mediated cAMP/PKA-MAPK pathway.

Kang T, Zhu L, Xue Y, Yang Q, Lei Q, Wang Q J Cell Mol Med. 2024; 28(11):e18366.

PMID: 38856956 PMC: 11163950. DOI: 10.1111/jcmm.18366.

Application of Multiomics Approach to Investigate the Therapeutic Potentials of Stem Cell-derived Extracellular Vesicle Subpopulations for Alzheimer's Disease.

Abyadeh M, Kaya A bioRxiv. 2024; .

PMID: 38798317 PMC: 11118424. DOI: 10.1101/2024.05.10.593647.

cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.

Zhang H, Liu Y, Liu J, Chen J, Wang J, Hua H J Hematol Oncol. 2024; 17(1):5.

PMID: 38233872 PMC: 10792844. DOI: 10.1186/s13045-024-01524-x.

References

Krenning L, Feringa F, Shaltiel I, van den Berg J, Medema R . Transient activation of p53 in G2 phase is sufficient to induce senescence. Mol Cell. 2014; 55(1):59-72. DOI: 10.1016/j.molcel.2014.05.007. View

Tucker S, Zorn A . The role of Popeye domain-containing protein 1 (POPDC1) in the progression of the malignant phenotype. Br J Pharmacol. 2021; 179(12):2829-2843. DOI: 10.1111/bph.15403. View

Palorini R, De Rasmo D, Gaviraghi M, Sala Danna L, Signorile A, Cirulli C . Oncogenic K-ras expression is associated with derangement of the cAMP/PKA pathway and forskolin-reversible alterations of mitochondrial dynamics and respiration. Oncogene. 2012; 32(3):352-62. DOI: 10.1038/onc.2012.50. View

Turnquist C, Horikawa I, Foran E, Major E, Vojtesek B, Lane D . p53 isoforms regulate astrocyte-mediated neuroprotection and neurodegeneration. Cell Death Differ. 2016; 23(9):1515-28. PMC: 5072428. DOI: 10.1038/cdd.2016.37. View

Mandal P, Saharan S, Tripathi M, Murari G . Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer's disease. Biol Psychiatry. 2015; 78(10):702-10. DOI: 10.1016/j.biopsych.2015.04.005. View

Gomez-Sintes R, Ledesma M, Boya P . Lysosomal cell death mechanisms in aging. Ageing Res Rev. 2016; 32:150-168. DOI: 10.1016/j.arr.2016.02.009. View

Sies H, Jones D . Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7):363-383. DOI: 10.1038/s41580-020-0230-3. View

Vannam R, Sayilgan J, Ojeda S, Karakyriakou B, Hu E, Kreuzer J . Targeted degradation of the enhancer lysine acetyltransferases CBP and p300. Cell Chem Biol. 2021; 28(4):503-514.e12. DOI: 10.1016/j.chembiol.2020.12.004. View

Kam T, Mao X, Park H, Chou S, Karuppagounder S, Umanah G . Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson's disease. Science. 2018; 362(6414). PMC: 6431793. DOI: 10.1126/science.aat8407. View

10.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

11.

Lei P, Ayton S, Finkelstein D, Spoerri L, Ciccotosto G, Wright D . Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med. 2012; 18(2):291-5. DOI: 10.1038/nm.2613. View

12.

Sripetchwandee J, Wongjaikam S, Krintratun W, Chattipakorn N, Chattipakorn S . A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloids-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload. Neuroscience. 2016; 332:191-202. DOI: 10.1016/j.neuroscience.2016.07.003. View

13.

Lewerenz J, Ates G, Methner A, Conrad M, Maher P . Oxytosis/Ferroptosis-(Re-) Emerging Roles for Oxidative Stress-Dependent Non-apoptotic Cell Death in Diseases of the Central Nervous System. Front Neurosci. 2018; 12:214. PMC: 5920049. DOI: 10.3389/fnins.2018.00214. View

14.

Insel P, Zhang L, Murray F, Yokouchi H, Zambon A . Cyclic AMP is both a pro-apoptotic and anti-apoptotic second messenger. Acta Physiol (Oxf). 2011; 204(2):277-87. PMC: 3125423. DOI: 10.1111/j.1748-1716.2011.02273.x. View

15.

Finkelstein D, Billings J, Adlard P, Ayton S, Sedjahtera A, Masters C . The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease. Acta Neuropathol Commun. 2017; 5(1):53. PMC: 5490188. DOI: 10.1186/s40478-017-0456-2. View

16.

Kurz T, Terman A, Gustafsson B, Brunk U . Lysosomes in iron metabolism, ageing and apoptosis. Histochem Cell Biol. 2008; 129(4):389-406. PMC: 2668650. DOI: 10.1007/s00418-008-0394-y. View

17.

Andrabi S, Dawson T, Dawson V . Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann N Y Acad Sci. 2008; 1147:233-41. PMC: 4454457. DOI: 10.1196/annals.1427.014. View

18.

Wang Y, Dawson V, Dawson T . Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol. 2009; 218(2):193-202. PMC: 2752872. DOI: 10.1016/j.expneurol.2009.03.020. View

19.

Song S, Xiao Z, Dekker F, Poelarends G, Melgert B . Macrophage migration inhibitory factor family proteins are multitasking cytokines in tissue injury. Cell Mol Life Sci. 2022; 79(2):105. PMC: 8799543. DOI: 10.1007/s00018-021-04038-8. View

20.

Wiggins S, Steegborn C, Levin L, Buck J . Pharmacological modulation of the CO/HCO/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase. Pharmacol Ther. 2018; 190:173-186. PMC: 6484840. DOI: 10.1016/j.pharmthera.2018.05.008. View