Is insulin-like growth factor-1 involved in Parkinson's disease development?

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder that results in the death of dopaminergic neurons within the substantia nigra pars compacta and the reduction in dopaminergic control over striatal output neurons, leading to a movement disorder most commonly characterized by akinesia or bradykinesia, rigidity and tremor. Also, PD is less frequently depicted by sensory symptoms (pain and tingling), hyposmia, sleep alterations, depression and anxiety, and abnormal executive and working memory related functions. On the other hand, insulin-like growth factor 1 (IGF-1) is an endocrine, paracrine and autocrine hormone with several functions including tissue growth and development, insulin-like activity, proliferation, pro-survival, anti-aging, antioxidant and neuroprotection, among others. Herein this review tries to summarize all experimental and clinical data to understand the pathophysiology and development of PD, as well as its clear association with IGF-1, supported by several lines of evidence: (1) IGF-1 decreases with age, while aging is the major risk for PD establishment and development; (2) numerous basic and translational data have appointed direct protective and homeostasis IGF-1 roles in all brain cells; (3) estrogens seem to confer women strong protection to PD via IGF-1; and (4) clinical correlations in PD cohorts have confirmed elevated IGF-1 levels at the onset of the disease, suggesting an ongoing compensatory or "fight-to-injury" mechanism.

Keywords: Aging; Central nervous system; Dopamine; Estrogens; IGF-1; Parkinson’s disease.

Fig. 1

Chronology of clinical symptoms in Parkinson’s disease (modified from Kalia et al. [8]). Schematic representation of the diagnosis (even 10 to 20 years before the onset of the disease) and motor/non-motor symptoms in early and advanced stages of Parkinson’s disease, with clinical and other iatrogenic symptoms

Fig. 2

Basal ganglia dysfunction and physiopathology of Parkinson’s disease. The progressive loss of ascending dopaminergic projections is the key factor in the establishment of Parkinson’s disease. Continuous lines represent the normal function of basal ganglia; dotted lines represent the normal function of brain segments without the previous inhibition/activation pathway; and red arrows represent the alterations in basal ganglia observed in PD

Fig. 3

Parallelism between the cellular and molecular mechanisms involved in the pathogenesis of Parkinson’s disease and IGF-1 deficiency (modified from Kalia et al. [8])