Current disease modifying approaches to treat Parkinson’s disease
Open accessAbstract
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.
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Motor dysfunction in clinical Parkinson's disease is primarily caused by an accelerated loss of substantia nigra pars compacta dopaminergic neurons.
“Since the motor dysfunction observed in clinical PD is primarily caused by an accelerated loss of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons”
From Mitochondrial DNA Damage in Substantia Nigra Pars Compacta Astrocytes Exacerbates Dopaminergic Neuron Loss in a 6-Hydroxydopamine Mouse Model of Parkinsonism (2026) · cites this paper as Lindholm et al. 2016
The Introduction (page unavailable) links clinical motor symptoms to declining dopamine levels and loss of dopaminergic neurons in the substantia nigra pars compacta. It does not describe that loss as accelerated or explicitly establish it as the primary cause of motor dysfunction. (LLM, conf=0.85)
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- Authors
- Lindholm, D., Mäkelä, J., Di Liberto, V., Mudò, G., Belluardo, N., Eriksson, O., & Saarma, M.
- Affiliations
- University of Helsinki (FI)
- University of Palermo (IT)
- Corresponding author
- Lindholm, Dan
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2015-11-30
- Volume
- 73
- Issue
- 7
- Pages
- 1365-1379
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11108524
- OpenAlex
- W2186612922
- Cited by
- 99
- References
- 7
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 10 · 2019: 13 · 2018: 15 · 2017: 23 · 2016: 11
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion, other-oa)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Funders
- Suomen Akatemia
- Jane ja Aatos Erkon Säätiö
- Michael J. Fox Foundation for Parkinson's Research
- Finnish Parkinson Foundation
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- Parkinson's disease, disease-modifying therapy, neurotrophic factors, glial cell line-derived neurotrophic factor, neurturin, CDNF, MANF, dopaminergic neuron survival, neuroprotection, mitochondrial dysfunction, neuroinflammation, L-DOPA, Parkinson's disease model
- MeSH terms
- Animals, Humans, Mitochondria, Nerve Growth Factors, Parkinson Disease, Recombinant Proteins, Neuroprotective Agents, Glial Cell Line-Derived Neurotrophic Factor, Neurturin, alpha-Synuclein, Unfolded Protein Response, Dopaminergic Neurons
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