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The neuroprotective action of lenalidomide on rotenone model of Parkinson's Disease: Neurotrophic and supportive actions in the substantia nigra pars compacta

Cankara, F. N., Günaydın, C., Bilge, S. S., Özmen, Ö. & Kortholt, A., 1-Nov-2020, In : Neuroscience Letters. 738, 7 p., 135308.

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  • The neuroprotective action of lenalidomide on rotenone model of Parkinson's Disease: Neurotrophic and supportive actions in the substantia nigra pars compacta

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  • Fatma Nihan Cankara
  • Caner Günaydın
  • Süleyman Sırrı Bilge
  • Özlem Özmen
  • Arjan Kortholt

Lenalidomide is a centrally active thalidomide analog that has potent anti-inflammatory and antiangiogenic activities. Currently, it is primarily used in the treatment of multiple myeloma and myelodysplastic syndromes. However, recent studies have revealed in addition to neuroprotection and neuromodulation of lenalidomide. Because of this combination of inflammation and neuro-immunogenic properties, lenalidomide is considered as a high potential compound for the treatment of neurodegenerative diseases. Despite intensive research during the last decade, the role of neurotrophic elements in the effect of lenalidomide is still not well understood. Therefore, in the current study, the effects of lenalidomide on neurodegeneration were investigated in a rotenone model of Parkinson's disease (PD) rat model. The PD rat model was generated by rotenone injection into the substantia nigra pars compacta (SNpc). After validation of the PD model, the rats were treated with lenalidomide (100 mg/kg) for 28 days. Our data shows that lenalidomide alleviated rotenone-induced motor impairments and deficits in dopamine-related behaviors and resulted in increased levels of tumor necrosis factor-α and calcium-binding protein B in the SNpc. Moreover, chronic lenalidomide treatment resulted increase in transforming growth factor immunoreactivity and brain derived neurotrophic factor expression in the SNPc. In addition, chronic treatment mitigated tyrosine hydroxylase expression prevented the rotenone-induced decrease in dopamine levels, and consequently a decrease in caspase-3/9 immunoreactivity. This thus shows that chronic lenalidomide treatment improves neuronal survival. Together with our data demonstrate that lenalidomide, in addition to its anti-inflammatory and immunomodulatory actions, is also capable of increasing neurotrophic factors in the SNpc, thereby preventing rotenone-induced motor impairments.

Original languageEnglish
Article number135308
Number of pages7
JournalNeuroscience Letters
Volume738
Early online date12-Sep-2020
Publication statusPublished - 1-Nov-2020

    Keywords

  • Lenalidomide, Neurodegeneration, Neurotrophins, Parkinson's disease, Rotenone

ID: 133867844