6533b7dbfe1ef96bd1270b57
RESEARCH PRODUCT
Current disease modifying approaches to treat Parkinson's disease
Mart SaarmaJohanna MäkeläNatale BelluardoGiuseppa MudòDan LindholmOve ErikssonValentina Di Libertosubject
0301 basic medicinemedicine.medical_specialtyParkinson's diseaseNeurturinNeurotrophic factorBiologySettore BIO/09 - Fisiologia03 medical and health sciencesCellular and Molecular Neuroscience0302 clinical medicineNeuroinflammationDopamineNeurotrophic factorsInternal medicineα-SynucleinmedicineGlial cell line-derived neurotrophic factorMolecular BiologyCerebral dopamine neurotrophic factorDopamine neuronPharmacologyDopaminergicCell Biologymedicine.diseaseDopamine neurons; ER stress; Mitochondria; Neuroinflammation; Neuropeptides; Neurotrophic factors; Protein aggregation; α-Synuclein; Molecular Medicine; Molecular Biology; Pharmacology; Cellular and Molecular Neuroscience; Cell Biology3. Good healthMitochondriaNeuropeptide030104 developmental biologyNerve growth factorEndocrinologybiology.proteinER streMolecular MedicineProtein aggregationNeuroscience030217 neurology & neurosurgerymedicine.drugdescription
Parkinson's disease (PD is a progressive neurological disorder characterized by the degeneration and death of midbrain dopamine and non-dopamine neurons in the brain leading to motor dysfunctions and other symptoms, which seriously influence the quality of life of PD patients. The drug L-dopa can alleviate the motor symptoms in PD, but so far there are no rational therapies targeting the underlying neurodegenerative processes. Despite intensive research, the molecular mechanisms causing neuronal loss are not fully understood which has hampered the development of new drugs and disease-modifying therapies. Neurotrophic factors are by virtue of their survival promoting activities attract candidates to counteract and possibly halt cell degeneration in PD. In particular, studies employing glial cell line-derived neurotrophic factor (GDNF) and its family member neurturin (NRTN), as well as the recently described cerebral dopamine neurotrophic factor (CDNF) and the mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown positive results in protecting and repairing dopaminergic neurons in various models of PD. Other substances with trophic actions in dopaminergic neurons include neuropeptides and small compounds that target different pathways impaired in PD, such as increased cell stress, protein handling defects, dysfunctional mitochondria and neuroinflammation. In this review, we will highlight the recent developments in this field with a focus on trophic factors and substances having the potential to beneficially influence the viability and functions of dopaminergic neurons as shown in preclinical or in animal models of PD.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-11-30 |