Polyamines in Parkinson's Disease: Balancing Between Neurotoxicity and Neuroprotection.
Annu Rev Biochem
; 92: 435-464, 2023 06 20.
Article
em En
| MEDLINE
| ID: mdl-37018845
ABSTRACT
The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways in PD pathogenesis, such as α-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Transtornos Parkinsonianos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Annu Rev Biochem
Ano de publicação:
2023
Tipo de documento:
Article