Neurotrophin mimetics and tropomyosin kinase receptors: a futuristic pharmacological tool for Parkinson's

Neurol Sci. 2023 Jul;44(7):2265-2275. doi: 10.1007/s10072-023-06684-1. Epub 2023 Mar 4.

Abstract

Parkinson's disease is a complex age-related progressive dopaminergic neurodegenerative disease consistently viewed as a disorder of movement and is characterized by its cardinal motor symptoms. While the motor symptoms and its clinical manifestations are attributed to the nigral dopaminergic neuronal death and basal ganglia dysfunction, studies have subsequently proven that the non-dopaminergic neurons in various brain regions are also additionally involved with the disease progression. Thus, it is now well accepted that the involvement of various neurotransmitters and other ligands accounts for the non-motor symptoms (NMS) associated with the Parkinson's disease. Consequently, this has demonstrated to possess remarkable clinical concerns to the patients in terms of various disability, such impaired to compromised quality of life and increased risk of morbidity and mortality. Currently, available pharmacological, non-pharmacological, and surgical therapeutic strategies neither prevent, arrest, nor reverse the nigral dopaminergic neurodegeneration. Thus, there is an imminent medical necessity to increase patient's quality of life and survival, which in turn decreases the incidence and prevalence of the NMS. The current research article reviews the potential direct involvement of neurotrophin and its mimetics to target and modulate neurotrophin-mediated signal transduction pathways to enlighten a new and novel therapeutic strategy along with the pre-existing treatments for Parkinson's disease and other neurological/neurodegenerative disorders which are associated with the downregulation of neurotrophins.

Keywords: Cholinergic transmission; Motor and non-motor symptoms; Neurotrophins; Small molecules; TrK receptors.

Publication types

  • Review

MeSH terms

  • Dopamine / metabolism
  • Dopaminergic Neurons
  • Humans
  • Nerve Growth Factors
  • Neurodegenerative Diseases* / drug therapy
  • Parkinson Disease*
  • Quality of Life
  • Signal Transduction / physiology

Substances

  • Nerve Growth Factors
  • tropomyosin kinase
  • Dopamine