The anti-hypertensive drug reserpine induces neuronal cell death through inhibition of autophagic flux

Kang Il Lee, Min Ju Kim, Hyongjong Koh, Jin I. Lee, Sim Namkoong, Won Keun Oh, Junsoo Park

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Abstract Reserpine is a well-known medicine for the treatment of hypertension and schizophrenia, but its administration can induce Parkinson's disease (PD)-like symptoms in humans and animals. Reserpine inhibits the vesicular transporter of monoamines and depletes the brain of monoamines such as dopamine. However, the cellular function of reserpine is not fully understood. In this report, we present one possible mechanism by which reserpine may contribute to PD-like symptoms. Reserpine treatment induced the formation of enlarged autophagosomes by inhibiting the autophagic flux and led to accumulation of p62, an autophagy adapter molecule. In particular, reserpine treatment increased the level of α-synuclein protein and led to accumulation of α-synuclein in autophagosomes. Treatment with rapamycin enhanced the effect of reserpine by further increasing the level of α-synuclein and neuronal cell death. Drosophila raised on media containing reserpine showed loss of dopaminergic neurons. Furthermore, cotreatment with reserpine and rapamycin aggravated the loss of dopaminergic neurons. Our results suggest that reserpine contributes to the loss of dopaminergic neurons by interfering with autophagic flux.

Original languageEnglish
Article number33895
Pages (from-to)402-408
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - 2015 Jun 12

Bibliographical note

Funding Information:
This study was supported by a National Research Foundation of Korea Grant funded by the Korean Government (2012R1A1A2042724) and by a grant from the Leading Space Core Technology Development Program through NRF funded by the Ministry of Science, ICT & Future Planning (2013M1A3A3A02042433).

Publisher Copyright:
© 2015 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'The anti-hypertensive drug reserpine induces neuronal cell death through inhibition of autophagic flux'. Together they form a unique fingerprint.

Cite this