Ageing is the main risk factor common to most primary neurodegenerative disorders. Indeed, age-related brain alterations have been long considered to predispose to neurodegeneration. Although protein misfolding and the accumulation of toxic protein aggregates have been considered as causative events in neurodegeneration, several other biological pathways affected by brain ageing also contribute to pathogenesis. Here, we discuss the evidence showing the involvement of the mechanisms controlling neuronal structure, gene expression, autophagy, cell metabolism and neuroinflammation in the onset and progression of neurodegenerative disorders. Furthermore, we review the therapeutic strategies currently under development or as future approaches designed to normalize these pathways, which may then increase brain resilience to cope with toxic protein species. In addition to therapies targeting the insoluble protein aggregates specifically associated with each neurodegenerative disorder, these novel pharmacological approaches may be part of combined therapies designed to rescue brain function.
Novel therapeutic approaches to target neurodegeneration / A.G. de la Fuente, S.C. Pelucchi, J. Mertens, M.M.G. Diluca, D. Mauceri, E. Marcello. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - (2023), pp. 1-24. [Epub ahead of print] [10.1111/bph.16078]
Novel therapeutic approaches to target neurodegeneration
S.C. PelucchiCo-primo
;M.M.G. Diluca;E. Marcello
Co-ultimo
2023
Abstract
Ageing is the main risk factor common to most primary neurodegenerative disorders. Indeed, age-related brain alterations have been long considered to predispose to neurodegeneration. Although protein misfolding and the accumulation of toxic protein aggregates have been considered as causative events in neurodegeneration, several other biological pathways affected by brain ageing also contribute to pathogenesis. Here, we discuss the evidence showing the involvement of the mechanisms controlling neuronal structure, gene expression, autophagy, cell metabolism and neuroinflammation in the onset and progression of neurodegenerative disorders. Furthermore, we review the therapeutic strategies currently under development or as future approaches designed to normalize these pathways, which may then increase brain resilience to cope with toxic protein species. In addition to therapies targeting the insoluble protein aggregates specifically associated with each neurodegenerative disorder, these novel pharmacological approaches may be part of combined therapies designed to rescue brain function.File | Dimensione | Formato | |
---|---|---|---|
22+Novel+therapeutic+approaches+to+target+neurodegeneration+ +Enhanced+Reader_compressed.pdf
accesso aperto
Descrizione: Invited Review
Tipologia:
Publisher's version/PDF
Dimensione
7.18 MB
Formato
Adobe PDF
|
7.18 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.