Postoperative neurocognitive disorders (PND) are the most common neurological disorders following surgery and anaesthesia before and within 12 months after surgery, with a high prevalence in the geriatric population. PND can severely deteriorate the quality of life of patients, especially among the elderly, mainly manifested as memory loss, attention, decline and language comprehension disorders, mostly in elderly patients, with an incidence as high as 31%. Previous studies have also raised the possibility of accelerated cognitive decline and underlying neuropathological processes associated with diseases that affect cognitive performance (e.g. Alzheimer's dementia) for reasons related to anaesthesia and surgery. Currently, most research on PND has focused on various molecular pathways, especially in the geriatric population. The various hypotheses that have been proposed regarding the mechanisms imply peripheral neuroinflammation, oxidative stress, mitochondrial homeostasis, synaptic function, autophagy disorder, blood-brain barrier dysfunction, the microbiota-gut-brain axis and lack of neurotrophic support. However, the underlying pathogenesis and molecular mechanisms of PND have not yet been uncovered. Recent research has focused on mitochondrial homeostasis. In this paper, we present a review of various studies to better understand and characterize the mechanisms of associated cognitive dysfunction. As the biochemical basis of PND becomes more clearly defined, future treatments based on mitochondrial homeostasis modulation can prove to be very promising.
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http://dx.doi.org/10.1080/07853890.2024.2411012 | DOI Listing |
Neurochem Res
January 2025
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Brain accumulation of the branched-chain α-keto acids α-ketoisocaproic acid (KIC), α-keto-β-methylvaleric acid (KMV), and α-ketoisovaleric acid (KIV) occurs in maple syrup urine disease (MSUD), an inherited intoxicating metabolic disorder caused by defects of the branched-chain α-keto acid dehydrogenase complex. Patients commonly suffer life-threatening acute encephalopathy in the newborn period and develop chronic neurological sequelae of still undefined pathogenesis. Therefore, this work investigated the in vitro influence of pathological concentrations of KIC (5 mM), KMV (1 mM), and KIV (1 mM) on mitochondrial bioenergetics in the cerebral cortex of neonate (one-day-old) rats.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.
Background: Mitophagy is a process of intracellular protein homeostasis through which cells eliminate senescent and dysfunctional mitochondria. Altered mitophagy contributes to Alzheimer´s disease (AD) pathology and is associated with worse cognitive functions. We evaluated association of levels of mitophagy proteins (ULK1, BNIP3L, PINK1, and TFEB in serum and ULK1 and PINK 1 in cerebrospinal fluid [CSF]) with spatial egocentric (body-centered) and allocentric (world-centered) navigation performance, which is typically impaired in early stages of AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Background: The choroid plexus (ChP) is formed by epithelial cells and stromal fibroblasts which act as a blood-cerebrospinal fluid (CSF) barrier, play a key role in maintaining brain homeostasis, and provide a niche for immune cells. ChP dysfunction has been implicated in Alzheimer's Disease (AD), including changes in CSF secretion, increased apoptosis, and dysregulated immune, mitochondrial, and transporter functions.
Method: Here, we performed single-nuclei RNA-Sequencing (snRNA-Seq) on 965,647 ChP nuclei from 68 ROSMAP participants with no cognitive impairment (NCI), mild cognitive impairment (MCI) or Alzheimer's Dementia (ADem).
Background: TAR-DNA-binding protein 43 (TDP43), is a pathologic marker in neurodegenerative diseases including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The aggregation of TDP-43, a crucial RNA-binding protein, is a consequence of post-translational modifications (PTMs) that disrupt its normal function. PTMs such as phosphorylation and ubiquitination contribute to the aberrant accumulation of TDP-43 aggregates, leading to neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).
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