Neurodegeneration-Disease and Dementia (original) (raw)
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IAR Journal of Medical Case Reports, 2021
The term neurodegenerative refers to diseases that are usually recognized by symptoms like decreased motor control, mood disorders, an d cognitive deficits. Some of the common neurodegenerative diseases are Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and the spinocerebellar ataxias. These diseases are complex and diverse in their pathophysiology with some causing memory and cognitive impairments and others affecting a person's ability to move, speak, control, and breathe. T here are some prevalent drugs and therapies, which seems to be effective in improving the disease condition. Thus, It is need of the hour to develop new and more effective therapeutic approaches and strategies to manage and potentially tackle these devastating neurodegenerative diseases.
Dopamine Receptors and Neurodegeneration
Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson's disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases.
Current and Potential Treatments of Parkinson's Disease
Parkinson's disease (PD), initially reported by James Parkinson in 1817, is a multisystem progressive neurodegenerative and a chronic disorder of the nervous system affecting the nerve cells. Although the aetiology of PD is still unknown, it primarily results from impaired dopaminergic neurons in the substantia nigra of the ventral mid-brain, located in the basal ganglia that controls balance and movement of the body. These nerve cells in the substantial nigra are the one responsible for production of Dopamine. The neurotransmitter dopamine is a chemical that transmits signals between neurons (or synapses) of the brain, which further possesses an effect on the rest of the body via the central nervous system. Dopamine plays a variety of roles in the brain such as voluntary movement, cognition, behaviour, sleep, mood, and working memory. Reduced dopamine activity in the substantia nigra pars compact (SNpc) with a successive loss of dopaminergic projections in the ventral striatum to both the putamen and caudate, causes an imbalance with other neurotransmitters leading a disarray of both motor and non-motor symptoms that become worse over time (Przedborski, 2003).
Strategies for the Treatment of Parkinson’s Disease: Beyond Dopamine
Frontiers in Aging Neuroscience
Parkinson's disease (PD) is the second-leading cause of dementia and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra alongside the presence of intraneuronal α-synuclein-positive inclusions. Therapies to date have been directed to the restoration of the dopaminergic system, and the prevention of dopaminergic neuronal cell death in the midbrain. This review discusses the physiological mechanisms involved in PD as well as new and prospective therapies for the disease. The current data suggest that prevention or early treatment of PD may be the most effective therapeutic strategy. New advances in the understanding of the underlying mechanisms of PD predict the development of more personalized and integral therapies in the years to come. Thus, the development of more reliable biomarkers at asymptomatic stages of the disease, and the use of genetic profiling of patients will surely permit a more effective treatment of PD.
Neurodegenerative dementia and Parkinsonism
The journal of nutrition, health & aging, 2010
Amyloid Precursor Protein serves a variety of physiological functions, including modulation of synaptic function, facilitation of neuronal growth and survival, protection against oxidative stress and surveillance against neuroactive compounds, toxins and pathogens. The APP gene is located on human chromosome 21. Alternative splicing of this gene provides different mRNAs which are translated into different APP isoforms. Two catabolic pathways have been described: the non-amyloïdogenic and the amyloïdogenic cascade. The first one leads to the extracellular soluble N-terminal part of the APP by α-secretase cleavage. The amyloïdogenic pathway results in the formation of the Aβ peptide by successive βsecretase and γ-secretase cleavages. The Aβ extracellular form is Aβ1-40, while the intraneuronal Aβ corresponds to Aβ1-42. In a pathological condition such as AD, the activation of the γsecretase pathway ends in an accumulation of Aβ with neurotoxic oligomers formation, then protofibrills and amyloid fibrils . Aggregation of Aβ, particularly Aβ1-42, into Abstract: Background: Dementia and Parkinsonism are two major neurodegenerative disorders. Accurate diagnosis can be difficult when patients have both syndromes because of a wide range of etiologies. Objectives: To improve clinical diagnosis, we propose a disease classification based on the pathological proteins which are involved in the neuropathological disease process. Design: Four neuropathological classes are proposed based on four major proteins, tau, Aβ, α-synuclein and TDP43 : 1/ Tauopathy and amyloidopathy with possible Parkinsonism, 2/ Tauopathy with predominant Parkinsonism, 3/ Synucleinopathies with cognitive impairment/dementia and 4/ The TAR DNA binding protein 43 . This classification raises certain questions in clinical practice due to intriguing overlaps between clinical presentations despite the same pathological protein being involved. Conclusion: The development of molecular and pathological protein research in neurodegenerative disorders can help classify the clinical association of dementia and Parkinsonism and improve therapeutic strategies against proteins involved in the degenerative process.
Will it Ever Become Possible to Prevent Dopaminergic Neuronal Degeneration?
Cns Neurological Disorders Drug Targets, 2008
Parkinson's disease (PD) is the second leading age-related degenerative brain disease in the world affecting millions of people. This neurological disorder disrupts the quality of life of patients and their families, exerts an enormous emotional and physical strain on caregivers, and has a large cost for society. Moreover, the increasing numbers of elderly people in the population will result in a sharp increase in the prevalence of PD. The understanding of its pathophysiology and treatment has advanced at a very impressive rate during past decades. Nevertheless, PD is still fatal and there is at present no cure for it. Furthermore, there are no proven therapies for prevention of PD and although evidence exists of risk and protective factors, this is not strong enough to warrant specific measures in an attempt to diminish risk or enhance protection. Drug development programmes are engaged in finding neuroprotective and neurorestorative therapies or, even better, discovering drugs able to rejuvenate the dopaminergic neurons. The latest developments in this promising field will be discussed with reference to the current literature together with the advantages and pitfalls of suggested drugs. Finally, an analysis of the role of various dietary recommendations, lifestyle, environmental and other factors in reducing the risk of PD is carried out.
Pathogenesis and Treatment of Parkinson's Disease
Academia Letters, 2021
The nervous system is unique in the vast complexity of thought processes and control actions it can perform. Defect or degeneration of any part of the nervous system leading to functional impairment. One of the neurodegenerative diseases is Parkinson's disease, the second most common neurodegenerative disease caused by the destruction of dopaminergic neurons from the substantia nigra. Destruction of substantia nigra leading to disturbance of dopamine distribution and causing parkinsonism symptoms and other functional impairment. The etiology of Parkinson's disease is still unknown, but environmental and genetic factors may influence the risk of Parkinson's disease. Although there is no definitive diagnosis of Parkinson's disease, it can be diagnosed historically and clinically. The most prominent pathological features of Parkinson's disease are loss of dopaminergic neurons in the substantia nigra and deposition of intraneuronal inclusions known as Lewy bodies. The symptoms of parkinsonism reflect a great diminished number of inhibitory dopaminergic neurons. Treatment of Parkinson's disease is aimed at restoring dopamine in the basal ganglia. The most common drugs used in Parkinson's disease are Levodopa which is the most potent and efficacious drug. Cathecol-O methyltransferase inhibitor and dopamine receptor agonist. A. Introduction to Parkinson's Disease Parkinson's disease (PD), known also as paralysis agitans, is one of neurodegenerative diseases, which results from widespread destruction of that portion of the substantia nigra (pars