Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease

Zhao, Yanxin; Haney, Matthew J.; Fallon, John K.; Rodriguez, Myosotys; Swain, Carson J.; Arzt, Camryn J.; Smith, Philip C.; Loop, Matthew S; Harrison, Emily B.; El‐Hage, Nazira; Batrakova, Elena V.

doi:10.3390/cells11121933

Cited by 11 publications

(8 citation statements)

References 60 publications

(96 reference statements)

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“…This intervention enhanced neuronal survival and behavioral traits. Along with that it reduced neuroinflammation . In a 6-OHDA rodent model of PD, GDNF injection presented neuroprotection and regeneration of DA neurons .…”

Section: Novel Targets For Improved Pd Therapeuticsmentioning

confidence: 80%

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Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Soni

Delvadia

Joharapurkar

et al. 2023

ACS Chem. Neurosci.

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Parkinson's disease (PD) is the second most prevailing progressive disorder leading to neurodegeneration, typically in people above 65 years of age. Motor clinical manifestations of PD appear in a much later stage and include rigidity, tremors, akinesia, and gait dysfunction. There are also nonmotor symptoms like GI and olfactory dysfunction. However, they cannot be considered for diagnosis of the disease, as they are unspecific. PD pathogenesis is mainly characterized by deposits of inclusion bodies on dopaminergic (DA) neurons in substantia nigra pars compacta region (SNpc) of the brain. The major component of these inclusion bodies, are αsynuclein aggregates. α-Synuclein undergoes misfolding and oligomerization to form aggregates and fibrils. These aggregates gradually propagate PD pathology. Other prominent features of this pathological development include mitochondrial dysfunction, neuroinflammation, oxidative stress, and impaired autophagy. These all contribute to neuronal degeneration. Besides this, there are many underlying factors which influence these processes. These factors comprise molecular proteins and signaling cascades. In this review, we have listed out underexplored molecular targets that may aid in development of neoteric and advanced therapeutics.

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Section: Novel Targets For Improved Pd Therapeuticsmentioning

confidence: 80%

“…Along with that it reduced neuroinflammation. 148 In a 6-OHDA rodent model of PD, GDNF injection presented neuroprotection and regeneration of DA neurons. 149 GDNF is inherently less stable, and hence therapeutic intervention is challenging.…”

Section: Glial Cell-line Derived Neurotrophic Factor (Gdnf)mentioning

confidence: 99%

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Soni

Delvadia

Joharapurkar

et al. 2023

ACS Chem. Neurosci.

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“…GDNF is known to increase neuronal survival. GDNF-enriched EVs treated with transgenic Parkin Q311 (X) Intranasal injection of a mouse enhanced neuronal survival, decreased neuroinflammation, and improved motor performance in the Parkinson’s disease animal model [ 261 ].…”

Section: Applications Of Evs As Nanotheranostic Targets In Cnsmentioning

confidence: 99%

Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions

Choi,

Chen,

Goldston

et al. 2024

Nano Convergence

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Central Nervous System (CNS) disorders represent a profound public health challenge that affects millions of people around the world. Diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and traumatic brain injury (TBI) exemplify the complexities and diversities that complicate their early detection and the development of effective treatments. Amid these challenges, the emergence of nanotechnology and extracellular vesicles (EVs) signals a new dawn for treating and diagnosing CNS ailments. EVs are cellularly derived lipid bilayer nanosized particles that are pivotal in intercellular communication within the CNS and have the potential to revolutionize targeted therapeutic delivery and the identification of novel biomarkers. Integrating EVs with nanotechnology amplifies their diagnostic and therapeutic capabilities, opening new avenues for managing CNS diseases. This review focuses on examining the fascinating interplay between EVs and nanotechnology in CNS theranostics. Through highlighting the remarkable advancements and unique methodologies, we aim to offer valuable perspectives on how these approaches can bring about a revolutionary change in disease management. The objective is to harness the distinctive attributes of EVs and nanotechnology to forge personalized, efficient interventions for CNS disorders, thereby providing a beacon of hope for affected individuals. In short, the confluence of EVs and nanotechnology heralds a promising frontier for targeted and impactful treatments against CNS diseases, which continue to pose significant public health challenges. By focusing on personalized and powerful diagnostic and therapeutic methods, we might improve the quality of patients.

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“…As expected, it was found that EVs collected from the conditioned media of GDNF-transfected macrophages contained GDNF proteins as well as genetic material-GDNF-encoding DNA. Moreover, applying GDNF-EVs via intranasal administration to the mouse model of Parkinson disease (transgenic Parkin Q311(X)A mice) led to a significant improvement in mobility, an increase in neuronal survival, and a decrease in neuroinflammation in mice [73].…”

Section: Genetic Engineering Of Donor Cellsmentioning

confidence: 99%

Strategies for Engineering of Extracellular Vesicles

Danilushkina,

Emene,

Barlev

et al. 2023

IJMS

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Extracellular vesicles (EVs) are membrane vesicles released by cells into the extracellular space. EVs mediate cell-to-cell communication through local and systemic transportation of biomolecules such as DNA, RNA, transcription factors, cytokines, chemokines, enzymes, lipids, and organelles within the human body. EVs gained a particular interest from cancer biology scientists because of their role in the modulation of the tumor microenvironment through delivering bioactive molecules. In this respect, EVs represent an attractive therapeutic target and a means for drug delivery. The advantages of EVs include their biocompatibility, small size, and low immunogenicity. However, there are several limitations that restrict the widespread use of EVs in therapy, namely, their low specificity and payload capacity. Thus, in order to enhance the therapeutic efficacy and delivery specificity, the surface and composition of extracellular vesicles should be modified accordingly. In this review, we describe various approaches to engineering EVs, and further discuss their advantages and disadvantages to promote the application of EVs in clinical practice.

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Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease

Cited by 11 publications

References 60 publications

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions

Strategies for Engineering of Extracellular Vesicles

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