New synaptic and molecular targets for neuroprotection in Parkinson's disease

Paolo Calabresi, Massimiliano Di Filippo, Antongiulio Gallina, Yingfei Wang, Jeannette N. Stankowski, Barbara Picconi, Valina L. Dawson, Ted M. Dawson

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

The defining anatomical feature of Parkinson's disease (PD) is the degeneration of substantia nigra pars compacta (SNc) neurons, resulting in striatal dopamine (DA) deficiency and in the subsequent alteration of basal ganglia physiology. Treatments targeting the dopaminergic system alleviate PD symptoms but are not able to slow the neurodegenerative process that underlies PD progression. The nucleus striatum comprises a complex network of projecting neurons and interneurons that integrates different neural signals to modulate the activity of the basal ganglia circuitry. In this review we describe new potential molecular and synaptic striatal targets for the development of both symptomatic and neuroprotective strategies for PD. In particular, we focus on the interaction between adenosine A2A receptors and dopamine D2 receptors, on the role of a correct assembly of NMDA receptors, and on the sGC/cGMP/PKG pathway. Moreover, we also discuss the possibility to target the cell death program parthanatos and the kinase LRRK2 in order to develop new putative neuroprotective agents for PD acting on dopaminergic nigral neurons as well as on other basal ganglia structures.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalMovement Disorders
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Parkinson Disease
Basal Ganglia
Corpus Striatum
Adenosine A2A Receptors
Neurons
Synaptic Potentials
Dopamine D2 Receptors
Dopaminergic Neurons
Neuroprotective Agents
Interneurons
Substantia Nigra
N-Methyl-D-Aspartate Receptors
Disease Progression
Dopamine
Cell Death
Phosphotransferases
Neuroprotection

Keywords

  • Dopamine receptors
  • LRRK2, Parthanatos
  • NMDA receptors
  • Synaptic plasticity

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Calabresi, P., Di Filippo, M., Gallina, A., Wang, Y., Stankowski, J. N., Picconi, B., ... Dawson, T. M. (2013). New synaptic and molecular targets for neuroprotection in Parkinson's disease. Movement Disorders, 28(1), 51-60. https://doi.org/10.1002/mds.25096

New synaptic and molecular targets for neuroprotection in Parkinson's disease. / Calabresi, Paolo; Di Filippo, Massimiliano; Gallina, Antongiulio; Wang, Yingfei; Stankowski, Jeannette N.; Picconi, Barbara; Dawson, Valina L.; Dawson, Ted M.

In: Movement Disorders, Vol. 28, No. 1, 01.01.2013, p. 51-60.

Research output: Contribution to journalReview article

Calabresi, P, Di Filippo, M, Gallina, A, Wang, Y, Stankowski, JN, Picconi, B, Dawson, VL & Dawson, TM 2013, 'New synaptic and molecular targets for neuroprotection in Parkinson's disease', Movement Disorders, vol. 28, no. 1, pp. 51-60. https://doi.org/10.1002/mds.25096
Calabresi P, Di Filippo M, Gallina A, Wang Y, Stankowski JN, Picconi B et al. New synaptic and molecular targets for neuroprotection in Parkinson's disease. Movement Disorders. 2013 Jan 1;28(1):51-60. https://doi.org/10.1002/mds.25096
Calabresi, Paolo ; Di Filippo, Massimiliano ; Gallina, Antongiulio ; Wang, Yingfei ; Stankowski, Jeannette N. ; Picconi, Barbara ; Dawson, Valina L. ; Dawson, Ted M. / New synaptic and molecular targets for neuroprotection in Parkinson's disease. In: Movement Disorders. 2013 ; Vol. 28, No. 1. pp. 51-60.
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