Protein and gene delivery systems for neurodegenerative disorders: Where do we stand today?

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

The role of melanin concentrating hormone neurons in appetite and reward regulation

İştah ve ödül algısı, fizyolojik birer durum olmanın yanı sıra, merkezi ve periferal sinir sisteminde bulunan çok karmaşık sinirsel ağlar tarafından kontrol edilmektedir. Hipotalamusta bulunan çekirdek ve alanların, enerji homeostazını düzenlediği ve ödül algısı yarattığı bilinmektedir. Lateral Hipotalamik Alan nöral alt gruplarından olan ve oreksijenik olduğu düşünülen Melanin Konsantre Eden Hormon (MCH) nöronları, önemli iştah ve ödül merkezleriyle sinaptik iletişim halinde bulunmakta, fakat etkisi ve rolü henüz bilinmemektedir. Bu çalışmada, MCH nöronlarının akut iştah ve ödül regülasyonu üzerindeki etkisi araştırılmıştır. Pmch-cre transgenik farelerin MCH nöronlarının akut aktivasyonunun ve inhibisyonunun kısa süreli iştah üzerindeki etkisi incelenmiştir. Elde edilen bulgular sonucunda, oreksijenik olduğu düşünülen bu nöronların, akut iştahı başlatmakta ve sürdürmekte yetersiz kaldığı belirlenmiştir. Optogenetik ve kemogenetik metotlar ile test edilen lokomotor aktivite düzeyinde bir farklılık saptanmamış; ancak MCH nöron baskılanmasının anksiyolitik etkileri olduğu gözlenmiştir. Ödül algısının anlaşılabilmesi için, MCH nöronlarının foto-uyarımı besin tüketimi ile eşleştirilmiş; tüketilen her besin için nöral aktivasyon sağlanınca besin tüketiminin arttığı anlaşılmıştır. Deneyler sonucunda bu nöronların iştahı etkilemediği tespit edildiğinden, gözlemlenen artışın MCH nöronlarının tetiklediği ödül algısından kaynaklanabileceği düşünülmüştür. Bu noktadan yola çıkılan deneylerde, besin veya post-oral bir ipucundan bağımsız olarak nöral aktivasyonun oto-uyarım olarak farelerin kontrole bırakılmasının, uyarım oranlarını anlamlı olarak arttığı tespit edilmiştir. Sonuç olarak, MCH nöronları akut iştahı başlatma ve sürdürmede yetersiz kalırken, bu nöronların uyarımının post-oral etmenlerden bağımsız olarak ödül algısını tetiklediği anlaşılmıştır.Appetite and reward perception, besides physiological regulation, is controlled by complex neural networks in central and peripheral nervous system. Nuclei and areas in the hypothalamus are known to regulate energy homeostasis and create a sense of reward. Melanin Concentrating Hormone (MCH) neurons of Lateral Hypothalamic Area are thought to be orexigenic due to their synaptic communication with important appetite and reward centers. Yet, the role of MCH neurons in appetite and reward regulation remained known. In this study, the effect of MCH neurons on acute appetite and reward regulation was investigated. The effect of acute activation and inhibition of MCH neurons on short-term appetite was studied. The findings demonstrated that MCH neurons, which were initially thought to be orexigenic, remained ineffective in triggering or sustaining the appetite. Locomotor activities and anxiety levels were tested with optogenetic and chemogenetic methods. No difference was observed in locomotor activity, yet MCH neural inhibition exhibited anxiolytic effects. In order to evaluate their role in reward mechanism, photo-stimulation of MCH neurons was paired with food, where significant increase in food consumption was detected. Since MCH neurons were found to be ineffective in appetite control, this increase pointed out their rewarding characteristic upon stimulation. Therefore, the post-oral cues were removed, and neural activation was offered as self-stimulation. Interestingly, in the absence of a post-oral cue, the rate of MCH neuron self-stimulation rate elevated significantly. Collectively, MCH neurons are insufficient to initiate or maintain acute appetite, yet their activation triggers reward mechanisms independent of post-oral cues

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

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