Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions

Autores
Martins, Waleska Kerllen; Silva, Maryana do Nascimento da; Pandey, Kiran; Maejima, Ikuko; Ramalho, Ercília; Olivon, Vania Claudia; Diniz, Susana Nogueira; Grasso, Daniel Hector
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases (15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field.
Fil: Martins, Waleska Kerllen. Anhanguera University; Brasil
Fil: Silva, Maryana do Nascimento da. Anhanguera University; Brasil
Fil: Pandey, Kiran. University of New York; Estados Unidos
Fil: Maejima, Ikuko. Gunma University; Japón
Fil: Ramalho, Ercília. Anhanguera University; Brasil
Fil: Olivon, Vania Claudia. Anhanguera University; Brasil
Fil: Diniz, Susana Nogueira. Anhanguera University; Brasil
Fil: Grasso, Daniel Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
Materia
ACTIVATION/INHIBITION OF AUTOPHAGY
AUTOPHAGY-TARGETED THERAPY
CANCER
CARDIAC OR CARDIOVASCULAR DISEASES
NEURODEGENERATIVE DISORDERS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/182065
Acceder
id CONICETDig_f149e1e1383552e1850e3e84dafc97e3
oai_identifier_str oai:ri.conicet.gov.ar:11336/182065
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directionsMartins, Waleska KerllenSilva, Maryana do Nascimento daPandey, KiranMaejima, IkukoRamalho, ErcíliaOlivon, Vania ClaudiaDiniz, Susana NogueiraGrasso, Daniel HectorACTIVATION/INHIBITION OF AUTOPHAGYAUTOPHAGY-TARGETED THERAPYCANCERCARDIAC OR CARDIOVASCULAR DISEASESNEURODEGENERATIVE DISORDERShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases (15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field.Fil: Martins, Waleska Kerllen. Anhanguera University; BrasilFil: Silva, Maryana do Nascimento da. Anhanguera University; BrasilFil: Pandey, Kiran. University of New York; Estados UnidosFil: Maejima, Ikuko. Gunma University; JapónFil: Ramalho, Ercília. Anhanguera University; BrasilFil: Olivon, Vania Claudia. Anhanguera University; BrasilFil: Diniz, Susana Nogueira. Anhanguera University; BrasilFil: Grasso, Daniel Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaElsevier2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/182065Martins, Waleska Kerllen; Silva, Maryana do Nascimento da; Pandey, Kiran; Maejima, Ikuko; Ramalho, Ercília; et al.; Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions; Elsevier; Current Research in Pharmacology and Drug Discovery; 2; 1-2021; 1-202590-2571CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2590257121000201info:eu-repo/semantics/altIdentifier/doi/10.1016/j.crphar.2021.100033info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:58Zoai:ri.conicet.gov.ar:11336/182065instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:48:59.264CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
title Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
spellingShingle Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
Martins, Waleska Kerllen
ACTIVATION/INHIBITION OF AUTOPHAGY
AUTOPHAGY-TARGETED THERAPY
CANCER
CARDIAC OR CARDIOVASCULAR DISEASES
NEURODEGENERATIVE DISORDERS
title_short Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
title_full Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
title_fullStr Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
title_full_unstemmed Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
title_sort Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions
dc.creator.none.fl_str_mv Martins, Waleska Kerllen
Silva, Maryana do Nascimento da
Pandey, Kiran
Maejima, Ikuko
Ramalho, Ercília
Olivon, Vania Claudia
Diniz, Susana Nogueira
Grasso, Daniel Hector
author Martins, Waleska Kerllen
author_facet Martins, Waleska Kerllen
Silva, Maryana do Nascimento da
Pandey, Kiran
Maejima, Ikuko
Ramalho, Ercília
Olivon, Vania Claudia
Diniz, Susana Nogueira
Grasso, Daniel Hector
author_role author
author2 Silva, Maryana do Nascimento da
Pandey, Kiran
Maejima, Ikuko
Ramalho, Ercília
Olivon, Vania Claudia
Diniz, Susana Nogueira
Grasso, Daniel Hector
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTIVATION/INHIBITION OF AUTOPHAGY
AUTOPHAGY-TARGETED THERAPY
CANCER
CARDIAC OR CARDIOVASCULAR DISEASES
NEURODEGENERATIVE DISORDERS
topic ACTIVATION/INHIBITION OF AUTOPHAGY
AUTOPHAGY-TARGETED THERAPY
CANCER
CARDIAC OR CARDIOVASCULAR DISEASES
NEURODEGENERATIVE DISORDERS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases (15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field.
Fil: Martins, Waleska Kerllen. Anhanguera University; Brasil
Fil: Silva, Maryana do Nascimento da. Anhanguera University; Brasil
Fil: Pandey, Kiran. University of New York; Estados Unidos
Fil: Maejima, Ikuko. Gunma University; Japón
Fil: Ramalho, Ercília. Anhanguera University; Brasil
Fil: Olivon, Vania Claudia. Anhanguera University; Brasil
Fil: Diniz, Susana Nogueira. Anhanguera University; Brasil
Fil: Grasso, Daniel Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina
description Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases (15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field.
publishDate 2021
dc.date.none.fl_str_mv 2021-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/182065
Martins, Waleska Kerllen; Silva, Maryana do Nascimento da; Pandey, Kiran; Maejima, Ikuko; Ramalho, Ercília; et al.; Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions; Elsevier; Current Research in Pharmacology and Drug Discovery; 2; 1-2021; 1-20
2590-2571
CONICET Digital
CONICET
url http://hdl.handle.net/11336/182065
identifier_str_mv Martins, Waleska Kerllen; Silva, Maryana do Nascimento da; Pandey, Kiran; Maejima, Ikuko; Ramalho, Ercília; et al.; Autophagy-targeted therapy to modulate age-related diseases: success, pitfalls, and new directions; Elsevier; Current Research in Pharmacology and Drug Discovery; 2; 1-2021; 1-20
2590-2571
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2590257121000201
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.crphar.2021.100033
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268947591725056
score 13.13397

Publicaciones similares