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Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by the accumulation of α-Synuclein aggregates and the degeneration of dopaminergic neurons in substantia nigra in the midbrain. Although the exact mechanisms of neuronal degeneration in PD remain largely elusive, various pathogenic factors, such as α-Synuclein cytotoxicity, mitochondrial dysfunction, oxidative stress, and pro-inflammatory factors, may significantly impair normal neuronal function and promote apoptosis. In this context, neuroinflammation and autophagy have emerged as crucial processes in PD that contribute to neuronal loss and disease development. They are regulated in a complex interconnected manner involving most of the known PD-associated genes. This review summarizes evidence of the implication of neuroinflammation and autophagy in PD and delineates the role of inflammatory factors and autophagy-related proteins in this complex condition. It also illustrates the particular significance of plasma and serum immune markers in PD and their potential to provide a personalized approach to diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: NGF is a molecule with a pleiotropic role, affecting neuro-immune functions, energy homeostasis, and synaptic plasticity. The mechanisms of NGF-induced neuronal differentiation are well established, but its effect on mitochondria in autism spectrum disorder (ASD) is still unclear. We hypothesize that NGF-induced neuronal development requires large amounts of energy, and mitochondria in ASD are overloaded to meet the new functional requirements. Method: The study includes primary diagnosed ASD children. Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from both patients and typically developing children (TDC). PBMCs were analyzed with Seahorse XFp, and plasma NGF protein levels were measured. Results: We detected nearly 50% higher NGF levels and approximately 40% elevation in spare respiratory capacity in ASD compared to TDC. These findings are consistent with the observed difference in maximal respiration, which was also significantly higher in the patient group. Both mitochondrial respiration and NGF plasma levels exhibit a strong potential to discriminate children with ASD from TDC. Conclusions: This study is the first to link elevated NGF with mitochondrial respiration and altered energy homeostasis in ASD. High NGF correlates with basic bioenergetic signatures that may be used as a screening tool to improve early diagnosis and clinical follow-up in ASD. [ABSTRACT FROM AUTHOR]

The purpose of this review is to summarize the current knowledge regarding the reciprocal associations between brain-derived neurotrophic factor (BDNF) and immune-inflammatory pathways and how these links may explain the involvement of this neurotrophin in the immune pathophysiology of mood disorders and schizophrenia. Toward this end, we delineated the protein–protein interaction (PPI) network centered around BDNF and searched PubMed, Scopus, Google Scholar, and Science Direct for papers dealing with the involvement of BDNF in the major psychosis, neurodevelopment, neuronal functions, and immune-inflammatory and related pathways. The PPI network was built based on the significant interactions of BDNF with neurotrophic (NTRK2, NTF4, and NGFR), immune (cytokines, STAT3, TRAF6), and cell–cell junction (CTNNB, CDH1) DEPs (differentially expressed proteins). Enrichment analysis shows that the most significant terms associated with this PPI network are the tyrosine kinase receptor (TRKR) and Src homology region two domain-containing phosphatase-2 (SHP2) pathways, tyrosine kinase receptor signaling pathways, positive regulation of kinase and transferase activity, cytokine signaling, and negative regulation of the immune response. The participation of BDNF in the immune response and its interactions with neuroprotective and cell–cell adhesion DEPs is probably a conserved regulatory process which protects against the many detrimental effects of immune activation and hyperinflammation including neurotoxicity. Lowered BDNF levels in mood disorders and schizophrenia (a) are associated with disruptions in neurotrophic signaling and activated immune-inflammatory pathways leading to neurotoxicity and (b) may interact with the reduced expression of other DEPs (CTNNB1, CDH1, or DISC1) leading to multiple aberrations in synapse and axonal functions. [ABSTRACT FROM AUTHOR]