Study effect mesenchymal stem cells and exosomes for Parkinson disease
Study effect mesenchymal stem cells and exosomes for Parkinson disease
Niloofar torkzadeh,1,*Mozhgan shirazi,2
1. Department of Biochemistry, Islamic Azad University, Falavarjan, Iran 2. Department of Biology, Scince and Reserch Branch, Islamic Azad, university, tehran, iran
Introduction: Parkinsons disease(PD) is the second most common neurodegenerative disorder nearly a ffecting 2% of the population over the age of 65. PD is characterized by a progressive loss of dopaminergic neurons of the substantia nigra/causing a number of motor symptoms to arise. Including tremors/ rigidity and bradykinesia with postural instability appearing in patients as the disease progresses. Another characteristic feature of PD is the existence of lewy bodies (LB) which are composed of the misfolded aggregates of αsynuclein(α-syn) protein.
Methods: We reviwed about 22 article were conducted frome 2018 to 2023 in the word and iran. We searched some key words such as mesenchymal stem cell, exosome, parkinsons disease, miRNA, cell and tissue therapy Elsevier, pubmed and SID
Results: In 2018, at leats 5 major autosomal dominant genes/ 5 autosomal recessive or x-linked factors and 11 monogenetic mutation for other disorders that present with parkinsonian like symptoms have been identified. The missense mutation (A53T) resulted in autosomal dominant PD inheritance that could be tracked through the hereditary line with almost full penetrance. Additionally, five other missense mutations to the SNCA gene, A30P, E46K, H50Q, G51D and G209A have also been reported with varying ages PD onset two genes phosphate and tensin homolog induced putative kinase1 (PINK1) and Daisuke Junko1(DJ-1) are of special interest because they are involved in neuronal survival under cellular stress. Additionaly an astute clinical observation of the comorbidity between gaucher disease (GD) and (PD) led researchers to examine other proteins with suspect. GD is an autosomal recessive disease resulting from homozygous mutations to housekeeping glucocerebrosidase gene(GBA). GBA alysosomal enzyme of the CNS, is thought to also have a role in protein aggregation in PD when mutated. Exosomes are EV derived from the endosomal complex. EVs are divided into three categories based on their size/ cargo and origin: exosomes microvesicles and apoptotic bodies. Phosphatidyl serine(PS) for exampls is involved in exosome sprouting and merging due to its enhanced flexibility. Lysosomal associated membrance protein(LAMP) tetraspanins (CD81, CD82, CD9, CD63) GTPase major histocompatibility complexΙ and Π (MHCΙ/Π) CD13 intercellular adhesion molecule1(ICAM1) fusion proteins such as tumor susceptibility gene 101 protein( TSG101) , annexin, integrin, heat shock protein 90(HSP90) and HSP70 are other molecules found abundantly in exosomal membranes. Messenger RNAs(mRNA) and microRNAs(miRNA) are also found in exosome and can carry genetic information to target cells. Exosomes produced from MSCs have also been found to contain cytokines and growth factors such as IL6, IL10, HGF and TGFβ1 all of them have role in regulating the immune system. Comparable quantitive of extracellular matrix metalloproteinase9 (MMP-9) and VEGF have been found in MSC derived exosomes all of which are important in inducing angiogenesis which may be essential for tissue repair. Exosomes containing modified α-syn siRNA reduced the amount of αsyn mRNA transcription and translation in the brain of transgenic mice. Moreover, exosomal shRNA minicircles to target αsyn in a PD mause model resulted in reduced Αsyn aggregation, decreased dopaminergic neuron death and improved clinical symptoms. Thus exosomes present a promising avenue for delivering therapeutic agents or genetic modulators to attenuate neuroinflammation in PD which may complement the cell therapy approach with iPSC derived dopaminergic neurons.
Conclusion: PD is the most common movement disorder, other movement disorders exist such as multiple system atrophy, progressive supranuclear palsy, chorea, ataxia and dystonia. Some movement disorders have similar symptoms to PD such as tremor, slow movement and rigidity .exosomes can affect gene expression and protein biological activity via receptor cells through the messenger RNAs and proteins that they carry. Furthermore exosomes from different sources carry different proteins and lipids and many exosome carry sprcific proteins. Levodopa/carbidopa, a combination medicine that increases the amount of dopamine in the brain, is the most common medication for PD (1). Doctors may use other medicines such as anticholinergics to reduce involuntary muscle movement.