Parkinsonism Treatment

Hennemann, Jana; Schatton, Wolfgang; Lyssy, Ralf H.

doi:10.1002/14356007.a19_001.pub2

Cited by 1 publication

(2 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, the loss of dopamine neuron bodies in the SNpc at the disease onset is only 30% . Moreover, some of the bodies of dopamine neurons remain in the brains of PD patients even at the very late stage (>20 years after the diagnosis), while dopamine axons in the putamen disappear almost completely within 5 years after diagnosis . Therefore, restoration of the axons of dopamine neurons in the putamen can be a valuable therapeutic strategy in PD.…”

Section: Resultsmentioning

confidence: 99%

“…With the global phenomenon of population aging, the number of PD cases is likely to grow significantly in the future. The major clinical diagnostic criteria for PD include tremor, rigidity, akinesia, postural instability, and bradyphrenia; depression is the most frequent psychopathological disorder . The diagnostic motor symptoms of PD are caused by progressive degeneration and death of dopamine neurons in the brain of affected people .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Small Molecule Supports the Survival of Cultured Dopamine Neurons and May Restore the Dopaminergic Innervation of the Brain in the MPTP Mouse Model of Parkinson’s Disease

Ardashov

Павлова

Mahato

et al. 2019

ACS Chem. Neurosci.

View full text Add to dashboard Cite

We previously showed that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2yl)cyclohex-3-ene-1,2-diol 1 alleviates motor manifestations of Parkinson's disease in animal models. In the present study, we designed and synthesized monoepoxides of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 and evaluated their biological activity in the MPTP mouse model of Parkinson's disease. We also assessed the ability of these compounds to penetrate the blood brain barrier (BBB). According to these data, we choose epoxide 4, which potently restored locomotor activity in MPTP-treated mice and penetrated the BBB with high efficacy, to further explore the potential mechanism of action. Epoxide 4 was found to robustly promote the survival of cultured dopamine neurons, protect dopamine neurons from toxin-induced degeneration and trigger the mitogen-activated protein kinase (MAPK) signaling cascade in cells of neuronal 2 origin. Meanwhile, neither survival-promoting effect nor MAPK activation was observed in nonneuronal cells treated with epoxide 4. In the MPTP mice model of Parkinson's disease, compound 4 increased the density of fibers expressing the key enzyme of dopamine synthesis, tyrosine hydroxylase. Taken together, these data indicate that epoxide 4 can be a promising compound for further development not only as symptomatic treatment but also as a disease-modifying drug to treat Parkinson's disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%