Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.
Alzheimer Disease/metabolism/pathology/physiopathology ; Animals ; Autophagy/*physiology ; Humans ; Huntington Disease/metabolism/pathology/physiopathology ; Models, Biological ; Neurodegenerative Diseases/metabolism/*pathology/physiopathology ; Neurons/*cytology ; Parkinson Disease/metabolism/pathology/physiopathology

Mitochondria are small organelles that produce the majority of cellular energy as ATP. Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD), and rare familial forms of PD provide valuable insight into the pathogenic mechanism underlying mitochondrial impairment, even though the majority of PD cases are sporadic. The regulation of mitochondria is crucial for the maintenance of energy-demanding neuronal functions in the brain. Mitochondrial biogenesis and mitophagic degradation are the major regulatory pathways that preserve optimal mitochondrial content, structure and function. In this mini-review, we provide an overview of the mitochondrial quality control mechanisms, emphasizing regulatory molecules in mitophagy and biogenesis that specifically interact with the protein products of three major recessive familial PD genes, PINK1, Parkin and DJ-1.
Adenosine Triphosphate ; Brain ; Homeostasis* ; Mitochondria ; Mitochondrial Degradation ; Neurons ; Organelles ; Parkinson Disease* ; Quality Control ; Organelle Biogenesis

A seventeen-year-old female patient was admitted with sudden-onset of headache and vomiting. Brain magnetic resonance imaging demonstrated a heterogeneously enhancing tumour in the left lateral ventricle. The tumour was removed and confirmed as a central neurocytoma (CN). For the residual tumour in the left lateral ventricle, gamma knife stereotactic radiosurgery was done at fifteen months after the initial surgery. Tumour recurred in the 4th ventricle at 5 yr after initial surgery. The tumour was removed and proved as a CN. In vitro primary culture was done with both tumours obtained from the left lateral ventricle and the 4th ventricle, respectively. Nestin, a neuronal stem cell marker was expressed in reverse Transcriptase-Polymerase Chain Reaction of both tumors. Both tumours showed different morphology and phenotypes of neuron and glia depending on the culture condition. When cultured in insulin, transferrin selenium and fibronectin media with basic fibroblast growth factors, tumour cells showed neuronal morphology and phenotypes. When cultured in the Dulbeco's Modified Essential Media with 20% fetal bovine serum, tumors cells showed glial morphology and phenotypes. It is suggested that CN has the characteristics of neuronal stem cells and potential to differentiate into mature neuron and glial cells depending on the environmental cue.
Brain Neoplasms/*pathology ; Cell Culture Techniques/methods ; Cell Differentiation ; Female ; Humans ; Neurocytoma/*pathology ; Stem Cells/*pathology ; Young Adult

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.
Adult ; Aneuploidy ; Blotting, Western ; Cell Line ; Diagnosis ; Dopaminergic Neurons ; Humans* ; Mesenchymal Stromal Cells* ; Mitochondria ; Parkinson Disease* ; Pituitary Neoplasms ; Plasmids ; Strikes, Employee ; Telomerase

BACKGROUND: Raising awareness and educating people regarding practices for skin cancer or melanoma prevention are critical in the context of the adversely increasing effects of global climate change. This study aimed to explore the knowledge, attitudes, and practices regarding skin cancer prevention and to determine the associated factors to knowledge, attitudes, and practices among dermatological patients in Vietnam. METHODS: This cross-sectional study included 590 dermatological patients between 18 and 82 years of age, who received an examination or treatment from the National Hospital of Dermatology in Hanoi, Vietnam, from September to December 2018. The respondents' attitudes on skin cancer and cancer prevention were assessed via face-to-face interviews with a structured questionnaire conducted by trained interviewers. RESULTS: Of the 590 respondents, the majority of people had correct responses to the question regarding skin cancer knowledge. Among the total participants, 39.8% thought that they were at risk of skin cancer, and 13.8% believed their occupation increased their skin cancer risk. The majority of respondents used hats (94.9%) and sunscreen skin coats (89.5%) and went into the shade (86.3%) when exposed to the sun. Women were less likely to be aware of their skin cancer risk but were more likely to practice prevention behaviors. CONCLUSION Our results show that dermatological patients have acceptable knowledge towards skin cancer prevention, but still need to change their behavior to prevent the risk of skin cancer. This study highlights the importance of education to raise awareness regarding skin cancer in order to promote practice prevention strategies for skin cancer in Vietnam.
Adult ; Aged ; Aged, 80 and over ; Cities ; Cross-Sectional Studies ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Melanoma ; prevention & control ; psychology ; Middle Aged ; Skin Diseases ; etiology ; Skin Neoplasms ; prevention & control ; psychology ; Vietnam ; Young Adult