FGF, Mechanism of Action, Role in Parkinson’s Disease, and Therapeutics

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease associated with severe disability and adverse effects on life quality. In PD, motor dysfunction can occur, such as quiescence, muscle stiffness, and postural instability. PD is also associated with autonomic nervous dysfunction, sleep disorders, psychiatric symptoms, and other non-motor symptoms. Degeneration of dopaminergic neurons in the substantia nigra compact (SNPC), Lewy body, and neuroinflammation are the main pathological features of PD. The death or dysfunction of dopaminergic neurons in the dense part of the substantia nigra leads to dopamine deficiency in the basal ganglia and motor dysfunction. The formation of the Lewy body is associated with the misfolding of α-synuclein, which becomes insoluble and abnormally aggregated. Astrocytes and microglia mainly cause neuroinflammation, and the activation of a variety of pro-inflammatory transcription factors and regulatory proteins leads to the degeneration of dopaminergic neurons. At present, PD is mainly treated with drugs that increase dopamine concentration or directly stimulate dopamine receptors. Fibroblast growth factor (FGF) is a family of cellular signaling proteins strongly associated with neurodegenerative diseases such as PD. FGF and its receptor (FGFR) play an essential role in the development and maintenance of the nervous system as well as in neuroinflammation and have been shown to improve the survival rate of dopaminergic neurons. This paper summarized the mechanism of FGF and its receptors in the pathological process of PD and related signaling pathways, involving the development and protection of dopaminergic neurons in SNPC, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. It provides a reference for developing drugs to slow down or prevent the potential of PD.

New developments in the biology of fibroblast growth factors

“…12.8.2 | Parkinson's and Huntington's disease Parkinson's disease (PD) is a neurodegenerative disorder that predominately affects dopaminergic neurons in the substantia nigra of the brain (Y. Liu, Deng, et al, 2021). Genetic association analysis indicates that polymorphisms in FGF20 may be significantly associated with an increased risk of PD in Chinese and Indian populations (Jing et al, 2015;Rudakou et al, 2021;Sadhukhan et al, 2018;X.…”

The FGF/FGFR system in the microglial neuroinflammation with Borrelia burgdorferi: intersectionality with other neurological conditions

“…FGF9 immunoreactivity was demonstrated in the brains of AD patients and those with MDD [54, 73]. It has protective roles in PD by downregulating oxidative stress, improving mitochondrial function and promoting neuronal survival [14]. Contrarily, it had pro-anxiety and depressive effects as exogenous administration increased these behaviors in rats [74].…”

“…; https://doi.org/10.1101/2022.08. 22.504844 doi: bioRxiv preprint others [11][12][13][14][15][16][17]. The FGFR family comprises 4 receptors FGFR1-4, which are transmembrane tyrosine kinases.…”

“…In recent years, the FGFR/ FGF system has been widely studied in several neurological diseases including AD, PD, depression, anxiety, multiple sclerosis, epilepsy, schizophrenia and others [11][12][13][14][15][16][17]. The FGFR family comprises 4 receptors FGFR1-4, which are transmembrane tyrosine kinases.…”

Apolipoprotein A-I mimetic peptides (ApoAI MP) improve oxidative stress and inflammatory responses in Parkinson’s disease mice

“…PD pathogenesis is closely related to many factors, such as environmental factors, genetic factors, aging and their interplay (Pang et al, 2019). The people aged ≥65 years have the high incidence of PD risk (1,500 out of 100,000 people) (Liu et al, 2021a), and the incidence of males is higher than that of females (Rocca, 2018). The clinical symptoms of PD include motor symptoms (resting tremor, rigidity, bradykinesia, etc.)…”