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Olfactory capacity declines with aging, but increasing evidence shows that smell dysfunction is one of the early signs of prodromal neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The study of olfactory ability and its role in neurodegenerative diseases arouses much interest in the scientific community. In neurology, olfactory impairment is a potential early marker for the onset of neurodegenerative diseases, but the underlying mechanism is poorly understood. The loss of smell is considered a clinical sign of early-stage disease and a marker of the disease's progression and cognitive impairment. Highlighting the importance of biological bases of smell and molecular pathways could be fundamental to improve neuroprotective and therapeutic strategies. We focused on the review articles and meta-analyses on olfactory and cognitive impairment. We depicted the neurobiology of olfaction and the most common olfactory tests in neurodegenerative diseases. In addition, we underlined the close relationship between the olfactory and cognitive deficit due to nasal neuroepithelium, which is a direct extension of the CNS in communication with the external environment. Neurons, Nose, and Neurodegenerative diseases highlights the role of olfactory dysfunction as a clinical marker for early stages of neurodegenerative diseases when it is associated with molecular, clinical, and neuropathological correlations.
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http://dx.doi.org/10.3390/ijms24032117 | DOI Listing |
Acta Neuropathol Commun
September 2025
Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.
Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.
View Article and Find Full Text PDFJ Neural Transm (Vienna)
September 2025
Parkinson's Foundation Centre of Excellence, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
Parkinson's disease patients are at increased risk of road traffic and car accidents and those with excessive daytime sleepiness are specially susceptible. Abnormal scores on the Epworth Sleepiness Scale predicts risk for driving-related somnolence which may cause road traffic accidents in driving patients as many such patients declare dozing of while in a car. Our study estimates that over 40% of patients with daytime somnolence have risks of dozing off in a car.
View Article and Find Full Text PDFNature
September 2025
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
As a key mitochondrial Ca transporter, NCLX regulates intracellular Ca signalling and vital mitochondrial processes. The importance of NCLX in cardiac and nervous-system physiology is reflected by acute heart failure and neurodegenerative disorders caused by its malfunction. Despite substantial advances in the field, the transport mechanisms of NCLX remain unclear.
View Article and Find Full Text PDFCytokine Growth Factor Rev
September 2025
Shandong University of Traditional Chinese Medicine, Jinan 250355, China; The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250001, China. Electronic address:
This review summarizes the biological properties of key myokines (Irisin, Apelin, CLCF1, and Myostatin) and osteokines (Osteocalcin, Sclerostin, FGF23 and the RANKL/OPG system). This work provides an in-depth analysis of the age-related network imbalance mechanism characterized by "downregulation of protective factors (Irisin, CLCF1, and uncarboxylated Osteocalcin) - upregulation of pro-degenerative factors (Myostatin, Sclerostin, and FGF23) - inflammation-driven amplification", and reveals the mechanism by which this network imbalance contributes to the comorbidity of sarcopenia, osteoporosis, and neurodegenerative diseases. Furthermore, the review evaluates the intersecting regulatory networks and molecular pathways through which myo-osteogenic factors modulate neurotrophic factors (BDNF, NGF and GDNF), and proposes intervention strategies based on these intersecting regulatory networks.
View Article and Find Full Text PDFBMJ Case Rep
September 2025
Gandhi Medical College and Hospital, Secunderabad, Telangana, India
Fahr's syndrome is a rare neurological condition marked by unusual calcifications in the basal ganglia and other brain regions, often resulting from metabolic disorders, such as hypoparathyroidism. Secondary hypoparathyroidism, a frequent complication of total thyroidectomy, can lead to Fahr's syndrome, manifesting as movement disorders, seizures, psychiatric symptoms and indications of calcium deficiency. This case report discusses a woman in her mid-30s who developed Fahr's syndrome due to secondary hypoparathyroidism after total thyroidectomy.
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