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Olfactory Biomarkers from Evolution to Sentinel of Neuropathologies and Opportunity for Window Therapeutics

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The olfactory system is one of the most conserved brain regions that allow animals to communicate with the external environment. Chemical signals are sorted and encoded by specialized olfactory receptor neurons which relay the electrical information to higher brain regions to elicit behavioral responses such ...

The olfactory system is one of the most conserved brain regions that allow animals to communicate with the external environment. Chemical signals are sorted and encoded by specialized olfactory receptor neurons which relay the electrical information to higher brain regions to elicit behavioral responses such as foraging for food, escaping from a predator, or mating, making sense of smell essential for reproduction and survival of the species.

Deficits of olfaction such as hyposmia, anosmia, hyperosmia, parosmia are conditions often co-symptomatic to neurological diseases or acute brain injury. Further, the topological organization of the olfactory nerve with direct endings in the nasal cavity without an interlining blood-brain barrier make this structure susceptible to neurotoxic chemical and microbial species that can propagate neuropathological events to the brain. This is consistent with the evidence that olfactory areas are the primary sites of neuronal network dysfunction in brain aging and progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and frontotemporal dementia.

The anatomical accessibility of the olfactory organ and its direct connection to the brain in the absence of a blood-brain barrier is increasingly considered for delivery of CNS drugs limiting off-target effects and with good compliance for the patient. Intranasal Insulin represents one of the most promising but "less hyped" disease-modifying drug for the treatment and prevention of Alzheimer's disease. This evidence reinforces the use of the nasal route for CNS therapeutics and sparks further pharmacological investigations to take advantage of this natural occurring window to the brain.

Despite the potential for exploiting the olfactory route in clinical diagnosis and therapeutics of CNS disease, the organ of smell has remained surprisingly overlooked. To increase the knowledge base surrounding chemosensation and promote the adoption of olfaction in preclinical and clinical settings, we welcome submissions of original research articles, review, minireview, opinion articles, and protocol articles on:

· Mechanisms of chemosensation from animals to humans
· Functional topology of peripheral and central olfactory areas
· The olfactory route as a port of entry for neurotoxic species
· Alteration of olfaction in neurological diseases
· Olfactory biomarkers in diagnostics
· Intranasal formulations for CNS therapy


Keywords: olfactory nerve, olfactory cortices, Alzheimer's disease, Parkinson's disease, intranasal drugs


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