Biomarker Detection and Therapy of Parkinson's and Alzheimer's disease using upconversion based approach: A Comprehensive Review.

Neurodegenerative diseases (NDs) are debilitating disorders characterized by the progressive and selective loss of function or structure in the brain and spinal cord. Both chronic and acute forms of these diseases are associated with significant morbidity and mortality, as they involve the degeneration of neurons in various brain regions. Misfolding and aggregation of amyloid proteins into oligomer and β-sheet rich fibrils share as common hallmark and lead to neurotoxicity. Unfortunately, effective curative therapies remain limited, underscoring the urgent need for early diagnosis and differentiation among disorders with overlapping symptoms to guide optimal clinical treatment strategies. Lack of selective probes for detecting soluble amyloid β-oligomer and insoluble amyloid deposits, for example, amyloid β1-42, α-synuclein or Tau proteins, promotes the onset of disease. A variety of sensors are being developed using the Förster resonance transfer mechanism (FRET) effect. However, its efficacy depends on fluorophore donors. Dyes also suffer several drawbacks, including photobleaching, interference from the aggregates, overlapping and blinking effects. Upconversion nanoparticles (UCNPs) solve such issues by acting as alternative fluorescence donors and helping in treating and diagnosing NDs at early stages. In this article, we present the theranostic potential of UCNPs and their critical challenges, along with the future direction. We begin with upconversion sensing mechanism followed with different biomarker detection of NDs using upconversion approach.