Infectious Diseases Causing Neuropathy

Bilbao, Juan M.; Schmidt, Robert E.

doi:10.1007/978-3-319-07311-8_11

Cited by 1 publication

(1 citation statement)

References 83 publications

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“…With a prevalence rate of 1% in adults and increasing to 7% after 55 years of age, they represent a significant public health concern worldwide [ 1 , 2 ]. The causes of peripheral neuropathies are diverse and encompass a wide range of factors, including traumatic injuries or nerve compression [ 3 , 4 ], diabetes mellitus, which affects between 25% to 50% of diabetics [ 5 ], exposure to toxins such as drug- and chemotherapy-induced neuropathy [ 6 ], infectious diseases [ 7 , 8 ], and vitamin imbalances [ 9 ]. The condition’s pathophysiology can include damage to small or large-diameter nerve fibers, neuronal cell bodies, and axons, as well as demyelination or an association of these factors.…”

Section: Introductionmentioning

confidence: 99%

Engineering Neurotoxin-Functionalized Exosomes for Targeted Delivery to the Peripheral Nervous System

Krishnan,

Alimi,

Pan

et al. 2024

Pharmaceutics

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The administration of therapeutics to peripheral nerve tissue is challenging due to the complexities of peripheral neuroanatomy and the limitations imposed by the blood–nerve barrier (BNB). Therefore, there is a pressing need to enhance delivery effectiveness and implement targeted delivery methods. Recently, erythrocyte-derived exosomes (Exos) have gained widespread attention as biocompatible vehicles for therapeutics in clinical applications. However, engineering targeted Exos for the peripheral nervous system (PNS) is still challenging. This study aims to develop a targeted Exo delivery system specifically designed for presynaptic terminals of peripheral nerve tissue. The clostridium neurotoxin, tetanus toxin-C fragment (TTC), was tethered to the surface of red blood cell (RBC)-derived Exos via a facile and efficient bio-orthogonal click chemistry method without a catalyst. Additionally, Cyanine5 (Cy5), a reactive fluorescent tag, was also conjugated to track Exo movement in both in vitro and in vivo models. Subsequently, Neuro-2a, a mouse neuronal cell line, was treated with dye-labeled Exos with/without TTC in vitro, and the results indicated that TTC-Exos exhibited more efficient accumulation along the soma and axonal circumference, compared to their unmodified counterparts. Further investigation, using a mouse model, revealed that within 72 h of intramuscular administration, engineered TTC-Exos were successfully transported into the neuromuscular junction and sciatic nerve tissues. These results indicated that TTC played a crucial role in the Exo delivery system, improving the affinity to peripheral nerves. These promising results underscore the potential of using targeted Exo carriers to deliver therapeutics for treating peripheral neuropathies.

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