Neuropeptide Modulation in Parkinson’s Disease
Summary
Neuropeptides constitute a diverse class of small protein mediators that influence neuronal survival, synaptic transmission and intracellular signalling. In Parkinson’s disease, the progressive loss of dopaminergic neurons in the substantia nigra pars compacta leads to characteristic motor dysfunction and a spectrum of non-motor symptoms. Accumulating evidence implicates neuropeptides such as ghrelin, neuropeptide Y, pituitary adenylate cyclase-activating polypeptide, substance P and neurotensin in the modulation of disease pathways. These peptides regulate mitochondrial bioenergetics, attenuate oxidative stress, inhibit apoptotic cascades and counteract neuroinflammatory processes. Mechanistic studies reveal that peptide–receptor interactions may restore autophagic flux, stabilise lysosomal function and prevent pathological protein aggregation, notably of α-synuclein oligomers. In parallel, changes in receptor expression on dopaminergic neurones have been linked to early synaptic dysfunction. The therapeutic potential of neuropeptide agonists and antagonists lies in their ability to engage multiple cellular targets and to cross-talk with classical dopaminergic and glutamatergic circuits. Global research efforts aim to translate these findings into disease-modifying interventions capable of slowing or halting neurodegeneration while also addressing non-motor disturbances such as gastrointestinal dysregulation and mood disorders.
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Neuropeptide Modulation in Parkinson’s Disease publication trend
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Technical terms
Neuropeptide: A small protein messenger released by neurons to modulate synaptic and intracellular signalling.
Substantia nigra pars compacta: Midbrain region rich in dopaminergic neurones that degenerate in Parkinson’s disease.
α-Synuclein oligomers: Pathogenic aggregated forms of the α-synuclein protein implicated in neuronal toxicity.
Autophagic flux: Dynamic process of autophagosome formation and clearance essential for cellular homeostasis.
Ghrelin receptor (GHSR): G-protein-coupled receptor mediating the effects of the hunger hormone ghrelin on neurone survival and metabolism.
References
- aSynPEP-DB: a database of biogenic peptides for inhibiting α-synuclein aggregation. Database (2023).
- The Emerging Role of Neuropeptides in Parkinson’s Disease. Frontiers in Aging Neuroscience (2021).
- Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia nigra contributes to Parkinson’s disease-like motor dysfunction. Molecular Brain (2018).
- Acylated Ghrelin is Protective Against 6-OHDA-induced Neurotoxicity by Regulating Autophagic Flux. Frontiers in Pharmacology (2021).
- Acyl-Ghrelin Attenuates Neurochemical and Motor Deficits in the 6-OHDA Model of Parkinson’s Disease. Cellular and Molecular Neurobiology (2022).
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