Protein and Gene Delivery Systems for Neurodegenerative Disorders: Where Do We Stand Today?

Abstract

It has been estimated that every year, millions of people are affected by neurodegenerative disorders, which complicate their lives and their caregivers’ lives. To date, there has not been an approved pharmacological approach to provide the complete treatment of neurodegenerative disorders. The only available drugs may only relieve the symptoms or slow down the progression of the disease. The absence of any treatment is quite rational given that neurodegeneration occurs by the progressive loss of the function or structure of the nerve cells of the brain or the peripheral nervous system, which eventually leads to their death either by apoptosis or necrotic cell death. According to a recent study, even though adult brain cells are injured, they can revert to an embryonic state, which may help to restore their function. These interesting findings might open a new path for the development of more efficient therapeutic strategies to combat devastating neurodegenerative disorders. Gene and protein therapies have emerged as a rapidly growing field for various disorders, especially neurodegenerative diseases. Despite these promising therapies, the complete treatment of neurodegenerative disorders has not yet been achieved. Therefore, the aim of this review is to address the most up-to-date data for neurodegenerative diseases, but most importantly, to summarize the available delivery systems incorporating proteins, peptides, and genes that can potentially target such diseases and pass into the blood–brain barrier. The authors highlight the advancements, at present, on delivery based on the carrier, i.e., lipid, polymeric, and inorganic, as well as the recent studies on radiopharmaceutical theranostics.

Neuroprotective Effect of Antiapoptotic URG7 Protein on Human Neuroblastoma Cell Line SH-SY5Y

“…In the first case, the use of specific molecules were used to inhibit or activate specific targets of the UPR (mainly the PERK pathway), resulting in an overall neuroprotective action. The use of recombinant viruses and/or protein and gene delivery systems [ 47 ] has become a promising emerging therapeutic option to avoid undesirable off-target pleiotropic effects in other organs, instead specifically targeting neurodegenerations. In this context, therefore, considering the promising results reported in this study and the further necessary evaluations that will certainly be carried out in the future, it is reasonable to also hypothesize the use of URG7 protein with this therapeutic target in neurodegenerative disorders such as Parkinson’s disease, where the pathological process affects numerous organs and tissues outside the brain [ 48 ].…”

Role of lysosome in healing neurological disorders by nano-bioengineering

“…The bi-modal effectiveness of nanotechnology-based carriers is undeniable, as not only they are ensuring targeted delivery to specific neuronal populations in particular affected brain regions, but also capable of protecting the molecular integrity of the modifiable and degradation-prone proteinaceous and genetic-materials. To this end, examples of nanoparticles are highlighted in Table 2 , which can either carry protein/peptide/genetic-materials/drugs in an encapsulated or surface conjugated manner ( Kang et al, 2018 ; Siafaka et al, 2022 ; Duan et al, 2023 ), to facilitate BBB-crossing to initiate localized treatment for neurodegeneration.…”

“…Based on these studies, the promising strategy of external-AA/ metabolite level modulation could be applied for treatment of neurodegenerative disorders. However, the wholistic AA/metabolite concentration change as well as global delivery of proteins and genetic materials (including, plasmids/DNA/shRNA/siRNA/miRNA; Siafaka et al, 2022;Duan et al, 2023), within a mixed neuronal-population could have limited efficacy, as region-specificity has been evidenced in 10.3389/fnins.2023.1331211 Frontiers in Neuroscience 06 frontiersin.org patient-brains in neurodegeneration. For example, HD affects the basal ganglia region, whereas hippocampal, entorhinal and cerebral cortical zone is affected in AD, substantia nigra is affected in PD and set of brain-spinal cord motor neurons are the vulnerable population in ALS.…”

The Major Hypotheses of Alzheimer’s Disease: Related Nanotechnology-Based Approaches for Its Diagnosis and Treatment

“…Gene therapy. In addition to drug delivery, nanoparticles can also be used to deliver genetic material to cells in the brain [246]. This approach, known as gene therapy, has the potential to target specific genes involved in the inflammatory response and modulate their expression.…”