The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications
The vascular endothelial growth factors (VEGFs) and their cognate receptors (VEGFRs), besides their well-known involvement in physiological angiogenesis/lymphangiogenesis and in diseases associated to pathological vessel formation, play multifaceted functions in the central nervous system (CNS). In...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661824000458 |
| _version_ | 1827338953009659904 |
|---|---|
| author | Claudia Ceci Pedro Miguel Lacal Maria Luisa Barbaccia Nicola Biagio Mercuri Grazia Graziani Ada Ledonne |
| author_facet | Claudia Ceci Pedro Miguel Lacal Maria Luisa Barbaccia Nicola Biagio Mercuri Grazia Graziani Ada Ledonne |
| author_sort | Claudia Ceci |
| collection | DOAJ |
| description | The vascular endothelial growth factors (VEGFs) and their cognate receptors (VEGFRs), besides their well-known involvement in physiological angiogenesis/lymphangiogenesis and in diseases associated to pathological vessel formation, play multifaceted functions in the central nervous system (CNS). In addition to shaping brain development, by controlling cerebral vasculogenesis and regulating neurogenesis as well as astrocyte differentiation, the VEGFs/VEGFRs axis exerts essential functions in the adult brain both in physiological and pathological contexts. In this article, after describing the physiological VEGFs/VEGFRs functions in the CNS, we focus on the VEGFs/VEGFRs involvement in neurodegenerative diseases by reviewing the current literature on the rather complex VEGFs/VEGFRs contribution to the pathogenic mechanisms of Alzheimer’s (AD) and Parkinson’s (PD) diseases. Thereafter, based on the outcome of VEGFs/VEGFRs targeting in animal models of AD and PD, we discuss the factual relevance of pharmacological VEGFs/VEGFRs modulation as a novel and potential disease-modifying approach for these neurodegenerative pathologies. Specific VEGFRs targeting, aimed at selective VEGFR-1 inhibition, while preserving VEGFR-2 signal transduction, appears as a promising strategy to hit the molecular mechanisms underlying AD pathology. Moreover, therapeutic VEGFs-based approaches can be proposed for PD treatment, with the aim of fine-tuning their brain levels to amplify neurotrophic/neuroprotective effects while limiting an excessive impact on vascular permeability. |
| first_indexed | 2024-03-07T19:43:03Z |
| format | Article |
| id | doaj.art-f6a935a1398e4e69a5cab9a9e54a7c70 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-07T19:43:03Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-f6a935a1398e4e69a5cab9a9e54a7c702024-02-29T05:18:10ZengElsevierPharmacological Research1096-11862024-03-01201107101The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implicationsClaudia Ceci0Pedro Miguel Lacal1Maria Luisa Barbaccia2Nicola Biagio Mercuri3Grazia Graziani4Ada Ledonne5Pharmacology Section, Department of Systems Medicine, University of Rome Tor Vergata, Rome, ItalyLaboratory of Molecular Oncology, IDI-IRCCS, Rome, ItalyPharmacology Section, Department of Systems Medicine, University of Rome Tor Vergata, Rome, ItalyNeurology Section, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; IRCCS Santa Lucia Foundation, Department of Experimental Neuroscience, Rome, Italy; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, USAPharmacology Section, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Corresponding author.Pharmacology Section, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; IRCCS Santa Lucia Foundation, Department of Experimental Neuroscience, Rome, Italy; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD, USAThe vascular endothelial growth factors (VEGFs) and their cognate receptors (VEGFRs), besides their well-known involvement in physiological angiogenesis/lymphangiogenesis and in diseases associated to pathological vessel formation, play multifaceted functions in the central nervous system (CNS). In addition to shaping brain development, by controlling cerebral vasculogenesis and regulating neurogenesis as well as astrocyte differentiation, the VEGFs/VEGFRs axis exerts essential functions in the adult brain both in physiological and pathological contexts. In this article, after describing the physiological VEGFs/VEGFRs functions in the CNS, we focus on the VEGFs/VEGFRs involvement in neurodegenerative diseases by reviewing the current literature on the rather complex VEGFs/VEGFRs contribution to the pathogenic mechanisms of Alzheimer’s (AD) and Parkinson’s (PD) diseases. Thereafter, based on the outcome of VEGFs/VEGFRs targeting in animal models of AD and PD, we discuss the factual relevance of pharmacological VEGFs/VEGFRs modulation as a novel and potential disease-modifying approach for these neurodegenerative pathologies. Specific VEGFRs targeting, aimed at selective VEGFR-1 inhibition, while preserving VEGFR-2 signal transduction, appears as a promising strategy to hit the molecular mechanisms underlying AD pathology. Moreover, therapeutic VEGFs-based approaches can be proposed for PD treatment, with the aim of fine-tuning their brain levels to amplify neurotrophic/neuroprotective effects while limiting an excessive impact on vascular permeability.http://www.sciencedirect.com/science/article/pii/S1043661824000458Parkinson’s diseaseAlzheimer’s diseaseVEGF-AVEGFR-1VEGFR-2Angiogenesis |
| spellingShingle | Claudia Ceci Pedro Miguel Lacal Maria Luisa Barbaccia Nicola Biagio Mercuri Grazia Graziani Ada Ledonne The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications Pharmacological Research Parkinson’s disease Alzheimer’s disease VEGF-A VEGFR-1 VEGFR-2 Angiogenesis |
| title | The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications |
| title_full | The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications |
| title_fullStr | The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications |
| title_full_unstemmed | The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications |
| title_short | The VEGFs/VEGFRs system in Alzheimer’s and Parkinson’s diseases: Pathophysiological roles and therapeutic implications |
| title_sort | vegfs vegfrs system in alzheimer s and parkinson s diseases pathophysiological roles and therapeutic implications |
| topic | Parkinson’s disease Alzheimer’s disease VEGF-A VEGFR-1 VEGFR-2 Angiogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824000458 |
| work_keys_str_mv | AT claudiaceci thevegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT pedromiguellacal thevegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT marialuisabarbaccia thevegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT nicolabiagiomercuri thevegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT graziagraziani thevegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT adaledonne thevegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT claudiaceci vegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT pedromiguellacal vegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT marialuisabarbaccia vegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT nicolabiagiomercuri vegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT graziagraziani vegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications AT adaledonne vegfsvegfrssysteminalzheimersandparkinsonsdiseasespathophysiologicalrolesandtherapeuticimplications |