Introduction. Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects. Methods. In the literature, we searched the clinical trials and followed up studies in humans, which have evaluated the effect of GH/IGF-1 on CNS and PNS. The following keywords have been used: “GH/IGF-1” associated with “neuroregeneration”, “amyotrophic lateral sclerosis”, “Alzheimer disease”, “Parkinson’s disease”, “brain”, and “neuron”. Results. Of the retrieved articles, we found nine articles about the effect of GH in healthy patients who suffered from traumatic brain injury (TBI), and six studies (four using IGF-1 and two GH therapy) in patients with amyotrophic lateral sclerosis (ALS). The administration of GH in patients after TBI showed a significantly positive recovery of brain and mental function. Treatment with GH and IGF-1 therapy in ALS produced contradictory results. Conclusions. Although strong findings have shown the positive effects of GH/IGF-1 administration on neuroregeneration in animal models, a very limited number of clinical studies have been conducted in humans. GH/IGF-1 therapy had different effects in patients with TBI, evidencing a high recovery of neurons and clinical outcome, while in ALS patients, the results are contradictory. More complex clinical protocols are necessary to evaluate the effect of GH/IGF-1 efficacy in neurodegenerative diseases. It seems evident that GH and IGF-1 therapy favors the optimal recovery of neurons when a consistent residual activity is still present. Furthermore, the effect of GH/IGF-1 could be mediated by, or be overlapped with that of other hormones, such as estradiol and testosterone.

VGF gene encodes for a neuropeptide precursor of 68 kDa composed by 615 (human) and 617 (rat, mice) residues, expressed prevalently in the central nervous system (CNS), but also in the peripheral nervous system (PNS) and in various endocrine cells. This precursor undergoes proteolytic cleavage, generating a family of peptides different in length and biological activity. Among them, TLQP-21, a peptide of 21 amino acids, has been widely investigated for its relevant endocrine and extraendocrine activities. The complement complement C3a receptor-1 (C3aR1) has been suggested as the TLQP-21 receptor and, in different cell lines, its activation by TLQP-21 induces an increase of intracellular Ca²⁺. This effect relies both on Ca²⁺ release from the endoplasmic reticulum (ER) and extracellular Ca²⁺ entry. The latter depends on stromal interaction molecules (STIM)-Orai1 interaction or transient receptor potential channel (TRPC) involvement. After Ca²⁺ entry, the activation of outward K⁺-Ca²⁺-dependent currents, mainly the K_Ca3.1 currents, provides a membrane polarizing influence which offset the depolarizing action of Ca²⁺ elevation and indirectly maintains the driving force for optimal Ca²⁺ increase in the cytosol. In this review, we address the main endocrine and extraendocrine actions displayed by TLQP-21, highlighting recent findings on its mechanism of action and its potential in different pathological conditions.

This study investigated modifications of microRNA expression profiles in knee synovial fluid of patients with osteoarthritis (OA) and rupture of the anterior cruciate ligament (ACL). Twelve microRNAs (26a-5p, 27a-3p, let7a-5p, 140-5p, 146-5p, 155-5p, 16-5p,186-5p, 199a-3p, 210-3p, 205-5p, and 30b-5p) were measured by real-time quantitative polymerase chain reaction (RT-qPCR) in synovial fluids obtained from 30 patients with ACL tear and 18 patients with knee OA. These 12 miRNAs were chosen on the basis of their involvement in pathological processes of bone and cartilage. Our results show that miR-26a-5p, miR-186-5p, and miR-30b-5p were expressed in the majority of OA and ACL tear samples, whereas miR-199a-3p, miR-210-3p, and miR-205-5p were detectable only in a few samples. Interestingly, miR-140-5p was expressed in only one sample of thirty in the ACL tear group. miR-140-5p has been proposed to modulate two genes (BGN and COL5A1100) that are involved in ligamentous homeostasis; their altered expression could be linked with ACL rupture susceptibility. The expression of miR-30b-5p was higher in OA and chronic ACL groups compared to acute ACL samples. We provide evidence that specific miRNAs could be detected not only in synovial fluid of patients with OA, but also in post-traumatic ACL tears.