Novel Therapies for Parkinsonian Syndromes–Recent Progress and Future Perspectives

Abstract

Background: Atypical parkinsonian syndromes are rare, fatal neurodegenerative diseases associated with abnormal protein accumulation in the brain. Examples of these syndromes include progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. A common clinical feature in parkinsonism is a limited improvement with levodopa. So far, there are no disease-modifying treatments to address these conditions, and therapy is only limited to the alleviation of symptoms. Diagnosis is devastating for patients, as prognosis is extremely poor, and the disease tends to progress rapidly. Currently, potential causes and neuropathological mechanisms involved in these diseases are being widely investigated.Objectives: The goal of this review is to summarize recent advances and gather emerging disease-modifying therapies that could slow the progression of atypical parkinsonian syndromes.Methods: PubMed and Google Scholar databases were searched regarding novel perspectives for atypical parkinsonism treatment. The following medical subject headings were used: “atypical parkinsonian syndromes—therapy,” “treatment of atypical parkinsonian syndromes,” “atypical parkinsonian syndromes—clinical trial,” “therapy of tauopathy,” “alpha-synucleinopathy treatment,” “PSP therapy/treatment,” “CBD therapy/treatment,” “MSA therapy/treatment,” and “atypical parkinsonian syndromes—disease modifying.” All search results were manually reviewed prior to inclusion in this review.Results: Neuroinflammation, mitochondrial dysfunction, microglia activation, proteasomal impairment, and oxidative stress play a role in the neurodegenerative process. Ongoing studies and clinical trials target these components in order to suppress toxic protein accumulation. Various approaches such as stem cell therapy, anti-aggregation/anti-phosphorylation agent administration, or usage of active and passive immunization appear to have promising results.Conclusion: Presently, disease-modifying strategies for atypical parkinsonian syndromes are being actively explored, with encouraging preliminary results. This leads to an assumption that developing accurate, safe, and progression-halting treatment is not far off. Nevertheless, the further investigation remains necessary.

Immunohistochemical Analysis of Mitochondrial Ferritin in the Midbrain of Patients with Parkinson’s Disease

“…FtMt expression is induced by hydrogen peroxide treatment causing oxidative stress in the cells [ 19 ]. Oxidative stress is a harmful factor in the body and is associated with neurodegenerative diseases including AD, PSP, and PD [ 9 , 16 , 20 ]. Previous studies reported that patients with AD had an increased level of FtMt expression in the temporal cortex [ 19 ] and in the SNc of patients with PSP [ 1 ].…”

Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders

“…GSK-3β may also be involved in neuronal apoptosis and mitochondrial activity ( Yang et al, 2017 ). Inhibition of GSK-3β was shown to protect dopaminergic neurons in various neurotoxic models of PD ( Petit-Paitel et al, 2009 ; Li et al, 2014 ) and is a target of ongoing drug development efforts ( Przewodowska et al, 2021 ). An analysis of crude extracts of Jurkat human T-cell leukemia clone E-6 cells revealed that incubation with PFF-A (and dieckol and eckol to lesser extent) inhibited GSK-3β activity ( Choi et al, 2015 ).…”

Label-Free Electrochemical Sensing Using Glassy Carbon Electrodes Modified with Multiwalled-Carbon Nanotubes Non-Covalently Functionalized with Human Immunoglobulin G

“…In addition, UA is an important natural antioxidant that demonstrates a relevant neuroprotective role in diseases related to oxidative stress. In fact, a low serum UA concentration has been associated with an increased risk of developing neurodegenerative diseases [48]. Thus, the efficient quantification of Do and UA is of great importance for human and animal health monitoring [49,50].…”