Aggresome formation and segregation of inclusions influence toxicity of α-synuclein and synphilin-1 in yeast

2011 ◽  
Vol 39 (5) ◽  
pp. 1476-1481 ◽  
Author(s):  
Erwin Swinnen ◽  
Sabrina Büttner ◽  
Tiago F. Outeiro ◽  
Marie-Christine Galas ◽  
Frank Madeo ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Elderly Population ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
The Elderly ◽  
Interacting Protein ◽  
Protein Deposits ◽  
Ring Complex ◽  
Aggresome Formation

PD (Parkinson's disease) is a neurodegenerative disorder, caused by a selective loss of dopaminergic neurons in the substantia nigra, which affects an increasing number of the elderly population worldwide. One of the major hallmarks of PD is the occurrence of intracellular protein deposits in the dying neurons, termed Lewy bodies, which contain different proteins, including aggregated α-synuclein and its interacting protein synphilin-1. During the last decade, a number of groups developed yeast models that reproduced important features of PD and allowed the deciphering of pathways underlying the cytotoxicity triggered by α-synuclein. Here, we review the recent contributions obtained with yeast models designed to study the presumed pathobiology of synphilin-1. These models pointed towards a crucial role of the sirtuin Sir2 and the chaperonin complex TRiC (TCP-1 ring complex)/CCT (chaperonin containing TCP-1) in handling misfolded and aggregated proteins.

The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer’s disease

2017 ◽  
Vol 28 (8) ◽  
Author(s):  
Yuan Zhang ◽  
Xu Chen ◽  
Yanfang Zhao ◽  
Murugavel Ponnusamy ◽  
Ying Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Degradation ◽  
Molecular Chaperones ◽  
Elderly Population ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Pathological Process ◽  
Β Amyloid

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly population. AD is associated with the buildup of β-amyloid and tau, which aggregate into extracellular plaques and neurofibrillary tangles. Although the exact mechanism of pathological process of AD is unclear, the dysfunction of protein degradation mechanisms has been proposed to play an important role in AD. The cellular degradation of abnormal or misfolded proteins consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy-lysosomal pathway (ALP), and interaction of molecular chaperones with UPS or ALP. Any disturbance to these systems causes proteins to accumulate, resulting in pathological process of AD. In this review, we summarize the knowledge of protein degradation pathways in the pathogenesis of AD in light of the current literature. In the future, the regulation UPS or ALP machineries could be the cornerstones of the treatment of AD.

scholarly journals Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 508
Author(s):  
Sara Silva ◽  
António J. Almeida ◽  
Nuno Vale
Keyword(s):  
Side Effects ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Pharmacokinetic Profile ◽  
The Elderly ◽  
Motor Symptoms ◽  
Administration Routes ◽  
Pharmaceutical Therapy ◽  
Drug Pharmacokinetic ◽  
The Brain

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

Gambaran Kejadian Tindakan Kekerasan pada Lansia : Literature Review

2021 ◽  
Vol 1 ◽  
pp. 1425-1436
Author(s):  
Dyah Pratiwi ◽  
Dyah Putri Aryati
Keyword(s):  
Literature Review ◽  
Elderly Population ◽  
Elder Abuse ◽  
The Elderly ◽  
Social Changes ◽  
Psychological Violence

AbstractThe increasing elderly population in Indonesia continues to grow. The elderly are individuals who experience physiological, psychological, and social changes. Therefore, the elderly is vulnerable to violence. Elder abuse persists in various areas in Indonesia. However, cases of elder abuse are often hidden because they are considered unimportant and the victims do not know where to report it. The purpose of this study was to describe the incidence of acts of violence in the elderly. The methodused in this study was a literature review by searching for articles in the PubMed and Google scolar database with the keyword: Elderly or Aged or Geriatric or Elder and Abuse or Violence with article limits from 2011-2020. There were five articles found. They had been critically reviewed using Strobe instruments. The results based on the five articles analysed showed some characteristics. Most of the respondents were 60-69 years old (50%), female (60%), education literate or primary (63%), married (67%), lived with other (59%), the elderly do not experience violence2.286, elderly experience violence 807, the type of violence that wa soften experienced by the elderly namely psychological violence is found to be (40%). Based on the five articles analysed, it can be concluded that the most violence experienced by the elderly is psychological violence. Therefore, the role of nurses is needed to provide services for families to prevent acts of violence in the elderly.Keywords: Elderly; persecution, violence AbstrakPeningkatan penduduk lansia di Indonesia terus bertambah. Lansia merupakan salah satu individu yang mengalami perubahan secara fisiologis, psikologis dan sosial sehingga lansia rentan mengalami tindakan kekerasan. Kekerasan terhadap lansia masih terjadi diberbagai wilayah di Indonesia. Namun, kasus kekerasan lansia kerap disembunyikan karena dianggap tidak penting dan korban tidak mengetahui lembaga yang dapat menerima laporan. Tujuan penelitian ini untuk mengetahui gambaran kejadian tindakan kekerasan pada lansia. Metode yang digunakan penelitian ini menggunakan literature review dengan mencari artikel pada database Pubmed dan Googlescholar dengan kata kunci :Elderly OR Aged OR Geriatric OR Elder AND Abuse ORViolencedengan batasan artikel dari 2011-2020 didapatkan 5 artikel yang telah dilakukan telaah kritis dengan menggunakan instrument Strobe. Hasil berdasarkan lima artikel yang dianalisa menunjukkan bahwa data karakteristik usia responden mayoritas 60-69 tahun yaitu (50%), berjenis kelamin perempuan sebanyak (60%), pendidikan literate or primarysebanyak (63%), berstatus menikah yaitu (67%), lived with other sebanyak (59%), lansia yang tidak mengalami kekerasan sebanyak 2.286, lansia yang mengalami kekerasan sebanyak 807 dan jenis kekerasan yang sering dialami lansia yaitu kekerasan psikologis didapatkan (40%). Berdasarkan dari kelima artikel yang dianalisa dapat disimpulkan bahwa kekerasan yang paling banyak dialami lansia yaitu kekerasan psikologis. Oleh sebab itu diperlukan peran perawat untuk memberikan pelayanan bagi keluarga untuk mencegah terjadinya tindakan kekerasan pada lansia.Kata kunci: Kekerasan; penganiayaan; usia lanjut

scholarly journals Decline in rates of clearance of IgG-sensitized erythrocytes with increasing age

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1726-1730
Author(s):  
KA Melez ◽  
LF Fries ◽  
BS Bender ◽  
T Quinn ◽  
MM Frank
Keyword(s):  
Aging Process ◽  
Elderly Population ◽  
The Elderly ◽  
Older Individuals ◽  
Immune Functions ◽  
Macrophage Function ◽  
Normal Volunteers ◽  
Age Related ◽  
Male Subjects

Decreased immune functions have been suggested as a cause for the increased incidence of autoimmunity, malignancy, and infection in the elderly population. To assess the possible role of changes in macrophage function in the aging process we studied the Fc receptor- mediated clearance of IgG-coated erythrocytes in 56 healthy normal volunteers by following the removal of radiolabeled autologous erythrocytes. An age-related decrease in Fc-mediated clearance rates in both female and male subjects was found, which suggests a physiological decline of this macrophage function in older individuals.

scholarly journals Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies

npj Vaccines ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Changyoun Kim ◽  
Armine Hovakimyan ◽  
Karen Zagorski ◽  
Tatevik Antonyan ◽  
Irina Petrushina ◽  
...  
Keyword(s):  
Dna Vaccines ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
The Elderly ◽  
Brain Regions ◽  
Dependent Manner ◽  
Lewy Neurites ◽  
The Brain

AbstractAccumulation of misfolded proteins such as amyloid-β (Aβ), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85–99 (PV-1947D), aa109–126 (PV-1948D), aa126–140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.

scholarly journals ROLE OF TRIVIDHA ROGAYATANA IN THE MANIFESTATION OF ESSENTIAL HYPERTENSION W.S.R. TO PRAGYAPARADA - A CONCEPTUAL STUDY

2021 ◽  
Vol 9 (8) ◽  
pp. 1733-1736
Author(s):  
Ajay Kumar Nigwal ◽  
Lajwanti Keswani ◽  
Rajesh Kumar Malviya ◽  
Arvind Kumar Yadav
Keyword(s):  
Elderly Population ◽  
Antihypertensive Drugs ◽  
Adult Population ◽  
The Elderly ◽  
Elevated Blood ◽  
The World ◽  
Causes Of Disease ◽  
Conceptual Study ◽  
Day By Day

Cardiovascular disease such as hypertension will be the largest cause of death and disability in India by 2020. The prevalence of hypertension is increasing globally and currently, more than 1 billion people have hypertension. About 26.4% of the world adult population in 2000 had hypertension and 29.2% were projected to have this con- dition by 2025. Elevated blood pressure affects 1 billion individuals and causes an estimated 10.4 million deaths per year. Thus, hypertension is needed to be studied. Though a lot of potent antihypertensive drugs are available today none of them is free from untoward adverse effects. Especially the elderly population poorly tolerates these drugs. The global incidence of hypertension is increasing day by day and is a very common problem nowadays. Ayurveda has classified the causes of disease into three main categories: - 1. Asatmendriyartha Samyoga 2. Pragyaparada and 3. Parinama (Kaala), these three main causes of disease enable different kinds of diseases to manifest. Firstly, they lead to the imbalance of body /or mind by vitiation the Tridosha. The consequence of the imbalance is a disturbance of the basic biological principles. Hypertension is a lifestyle disorder. Ayurveda causes of lifestyle disorders are mainly Pragyaparada. Pragyaparadha is the main cause of all noncommunicable dis- eases (NCDs) such as diabetes, cancer, hypertension etc. Keywords: Asatmendriyartha, Pragyaparada, Parinama, Trividha Rogaayatanas, Hypertension.

Parkinson's Disease Genetics and Pathophysiology

2021 ◽  
Vol 44 (1) ◽  
pp. 87-108
Author(s):  
Gabriel E. Vázquez-Vélez ◽  
Huda Y. Zoghbi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Disease Risk ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Disease Modifying ◽  
Common Neurodegenerative Disorder

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.

The Role of Novel Bone Forming Agents in the Treatment of Osteoporosis

2020 ◽  
pp. 089719002096122
Author(s):  
Hansita B. Patel ◽  
Lynsie J. Lyerly ◽  
Cheryl K. Horlen
Keyword(s):  
Elderly Population ◽  
Cost Effective ◽  
The Elderly ◽  
Bisphosphonate Therapy ◽  
Evidence Based ◽  
First Line ◽  
Treatment Of Osteoporosis ◽  
Cost Effective Treatment

Osteoporosis is a growing epidemic that leads to significant morbidity and mortality among the elderly population due to associated fractures that lead to disabilities and reduced quality of life. Bisphosphonates are well-established as a first-line and cost-effective treatment for osteoporosis. Unfortunately, clinicians are often uncertain as to how to select treatments when bisphosphonates are ineffective as initial treatment or contraindicated. Romosozumab and abaloparatide are 2 alternative agents that have been recently FDA approved for the treatment of osteoporosis in postmenopausal women at high risk for fracture or patients who have failed or are intolerant to other osteoporosis therapies. Currently, the National Osteoporosis Foundation (NOF) has no formal recommendations in regard to these 2 novel agents. The purpose of this review is to help guide pharmacists on how to ensure appropriate utilization of these 2 novel bone-forming agents as potential alternatives to bisphosphonate therapy by providing evidence-based recommendations according to the current literature and key counseling points.

scholarly journals The Role of Spinal Orthoses in Osteoporotic Vertebral Fractures of the Elderly Population (Age 60 Years or Older): Systematic Review

2020 ◽  
pp. 219256822094803
Author(s):  
Barry Ting Sheen Kweh ◽  
Hui Qing Lee ◽  
Terence Tan ◽  
Joost Rutges ◽  
Travis Marion ◽  
...  
Keyword(s):  
Systematic Review ◽  
Elderly Patients ◽  
Vertebral Fractures ◽  
Postural Stability ◽  
Elderly Population ◽  
The Elderly ◽  
Functional Improvement ◽  
Osteoporotic Vertebral Fractures ◽  
Spinal Orthoses

Study Design: Systematic review. Objective: Spinal orthoses have been generally used in the management of osteoporotic vertebral fractures in the elderly population with purported positive biomechanical and functional effects. To our knowledge, this is the first systematic review of the literature examining the role of spinal orthoses in osteoporotic elderly patients who sustain low energy trauma vertebral fractures. Methods: A systematic literature review adherent to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Methodical searches utilizing MEDLINE, EMBASE, Google Scholar, and Cochrane Databases was performed. Results: Of the 2019 articles initially retrieved, 7 published articles (4 randomized controlled trials and 3 prospective cohort studies) satisfied the inclusion criteria. Five studies reported improvement in quantitative measurements of spinal column stability when either a rigid or semirigid orthosis was used, while 1 study was equivocal. The studies also showed the translation of biomechanical benefit into significant functional improvement as manifested by improved postural stability and reduced body sway. Subjective improvement in pain scores and quality of life was also noted with bracing. Conclusion: The use of spinal orthoses in neurologically intact elderly patients aged 60 years and older with osteoporotic compression vertebral fractures results in improved biomechanical vertebral stability, reduced kyphotic deformity, enhanced postural stability, greater muscular strength and superior functional outcomes.

scholarly journals Alzheimer’s Pathogenesis and Its Link to the Mitochondrion

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
C. Simoncini ◽  
D. Orsucci ◽  
E. Caldarazzo Ienco ◽  
G. Siciliano ◽  
U. Bonuccelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cognitive Functions ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Mitochondria Dysfunction ◽  
Neurodegenerative Process ◽  
Mitochondrial Impairment ◽  
And Oxidative Stress

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. This neurodegenerative disorder is clinically characterized by impairment of cognitive functions and changes in behaviour and personality. The pathogenesis of AD is still unclear. Recent evidence supports some role of mitochondria dysfunction and oxidative stress in the development of the neurodegenerative process. In this review, we discuss the role of mitochondrial dysfunction in AD, focusing on the mechanisms that lead to mitochondrial impairment, oxidative stress, and neurodegeneration, a “vicious circle” that ends in dementia.

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