The Gut-Brain Axis in Alzheimer's and Parkinson's Diseases: The Catalytic Role of Mitochondria.

Accumulating evidence suggests that gut inflammation is implicated in neuroinflammation in Alzheimer's and Parkinson's diseases. Despite the numerous connections it remains unclear how the gut and the brain communicate and whether gut dysbiosis is the cause or consequence of these pathologies. Importantly, several reports highlight the importance of mitochondria in the gut-brain axis, as well as in mechanisms like gut epithelium self-renewal, differentiation, and homeostasis. Herein we comprehensively address the important role of mitochondria as a cellular hub in infection and inflammation and as a link between inflammation and neurodegeneration in the gut-brain axis. The role of mitochondria in gut homeostasis and as well the crosstalk between mitochondria and gut microbiota is discussed. Significantly, we also review studies highlighting how gut microbiota can ultimately affect the central nervous system. Overall, this review summarizes novel findings regarding this cross-talk where the mitochondria has a main role in the pathophysiology of both Alzheimer's and Parkinson's disease strengthen by cellular, animal and clinical studies.

Nocardia cyriacigeorgica Elicits Gut Disturbances in a Leaky Gut Model of Colitis, but Not the Harmful Cascade Leading to Gut-First Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with an unknown cause. Recent research has highlighted the importance of the gut in neuronal and immune maturation through the exchange of nutrients and cellular signals. This has led to the "gut-first PD" hypothesis, which aims to explain many of the sporadic cases and their prodromal intestinal symptoms, such as constipation and intestinal α-synuclein (aSyn) aggregation. The link between mitochondrial dysfunction and aSyn deposition is central to PD pathophysiology, since they can also trigger pro-inflammatory signals associated with aSyn deposition, potentially contributing to the onset of PD. As mitochondria are derived from ancestral alpha-proteobacteria, other bacteria may specifically target this organelle. We sought to use Nocardia cyriacigeorgica, a bacterium previously associated with parkinsonism, and dextran sulfate sodium (DSS) as pro-inflammatory modulators to gain further insight into the onset of PD. This study indicates that aSyn aggregation plus mitochondrial dysfunction without intestinal barrier leakage are not sufficient to trigger gut-first PD.

Neuro-immune interactions in health and disease: Insights from FENS-Hertie 2022 Winter School.

In a great partnership, the Federation of European Neuroscience Societies (FENS) and the Hertie Foundation organized the FENS-Hertie 2022 Winter School on 'Neuro-immune interactions in health and disease'. The school selected 27 PhD students and 13 postdoctoral fellows from 20 countries and involved 14 faculty members experts in the field. The Winter School focused on a rising field of research, the interactions between the nervous and both innate and adaptive immune systems under pathological and physiological conditions. A fine-tuned neuro-immune crosstalk is fundamental for healthy development, while disrupted neuro-immune communication might play a role in neurodegeneration, neuroinflammation and aging. However, much is yet to be understood about the underlying mechanisms of these neuro-immune interactions in the healthy brain and under pathological scenarios. In addition to new findings in this emerging field, novel methodologies and animal models were presented to foment research on neuro-immunology. The FENS-Hertie 2022 Winter School provided an insightful knowledge exchange between students and faculty focusing on the latest discoveries in the biology of neuro-immune interactions while fostering great academic and professional opportunities for early-career neuroscientists from around the world.

The Mitochondrial Ribosome: A World of Opportunities for Mitochondrial Dysfunction Toward Parkinson's Disease.

Significance: Mitochondrial ribosomes (mitoribosomes) are organelles that translate mitochondrial messenger RNA in the matrix and, in mammals, have evolved to translate 13 polypeptides of the pathway that performs oxidative phosphorylation (OXPHOS). Although a number of devastating diseases result from defects in this mitochondrial translation apparatus, most are associated with genetic mutations and little is known about allelopathic defects caused by antibiotics, toxins, or nonproteinogenic amino acids. Recent Advances: The levels of mitochondrial ribosomal subunits 12S and 16S ribosomal RNA (rRNA) in cells/tissues from patients carrying mutations in these genes have been associated with alterations in mitochondrial translation efficiency and with impaired OXPHOS activities, as well as with the severity of clinical phenotypes. In recent decades, important studies revealed a prominent role of mitochondrial dysfunction in Parkinson's disease (PD); however, the involvement of mitoribosomes remains largely unknown. Critical Issues: Considering that mitoribosomal structure and function can determine the efficiency of OXPHOS and that an impaired mitochondrial respiratory chain is a common finding in PD, we argue that the mitoribosome may be key to disease onset and progression. With this review, we comprehensively integrate the available knowledge on the composition, assembly, and role of the mitoribosome in mitochondrial efficiency, reflecting on its possible involvement in the etiopathogenesis of this epidemic disease as an appealing research avenue. Future Directions: If a direct correlation between mitoribosome failure and PD pathology is demonstrated, these mitochondrial organelles will provide valuable early clinical markers and potentially attractive targets for the development of innovative PD-directed therapeutic agents.