Promising Targets for the Treatment of Neurodegenerative Diseases

Abstract

Genetics and pathology have proven to be an effective combination to identify an evolving and deepening landscape of pathways and potential therapeutic targets in neurodegenerative diseases. Initially this landscape appeared to be populated with distinct therapeutic targets but with potentially overlapping mechanisms in each neurodegenerative disease. Our understanding has expanded to recognize that multiple pathologies are common in neurodegenerative disease, and that there is considerable overlap in pathways and targets driving neurodegenerative diseases. This potentially opens the way for future treatments to be indicated by tissue pathology and genetic basis rather than clinical phenotype. The potential to treat neurodegenerative disease by addressing underlying pathophysiology is still in the early days and challenges remain, especially the likely need to address pathologies early in disease. This will require redefinition of diagnosis and the tools to enable earlier diagnosis.

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

“…Alzheimer's disease (AD) was first described by Dr. Alois Alzheimer in 1906, and since then it has been one the most representative and intriguing neurodegenerative pathologies of the central nervous system (CNS) . It is the most common type of dementia and usually manifests clinically with initial amnesia, characterized by the inability to form recent memories, as well as with cognitive impairment .…”

“…that performs an important role or is related to some signaling pathway affecting the disorder. In addition to these biological targets mentioned above, many others have also been related to AD pathophysiological hypotheses and all have been used in AD drug discovery studies, including those involving in silico methods, also known as computer‐aided drug design (CADD) …”

“…Alzheimer's disease (AD) was first described by Dr.A lois Alz-heimerin1906, andsince then it has been one the mostrepresentativea nd intriguing neurodegenerativep athologies of the central nervous system (CNS). [1][2][3] It is the most common type of dementia and usuallym anifestsc linically with initial amnesia, characterizedb yt he inability to form recent memories, as well as with cognitive impairment. [4,5] It is al ong-term and slowly progressive disorder that may also bring about symptoms such as difficulty in solving logic problems, declineinlanguage skills, and, in some cases, psychosis, anxiety,d epression, and other psychological symptoms.…”

“…that performs an importantr ole or is related to some signaling pathway affecting the disorder.I na ddition to theseb iological targets mentioned above, many othersh ave also been relatedt oA Dp athophysiological hypotheses and all have been used in AD drug discovery studies, including those involving in silico methods, also known as computer-aided drugdesign (CADD). [1,8,23,24] The CADD of new potentiall igands that show biological activity or affinity toward AD targets is very promising,a sr eviewedr ecently. [25][26][27][28] Nevertheless, few of these reports are focused on the mechanism of action,n or do they consider the possibility of alternative mechanisms that occur betweent hese ligandsa nd the corresponding targets.…”

Evaluating the current state of Mendelian randomization studies: a protocol for a systematic review on methodological and clinical aspects using neurodegenerative disorders as outcome

“…Neurodegeneration, which occurs in diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), multiple sclerosis (MS), and Parkinson’s disease (PD), is characterized by diverse pathological conditions and heterogeneous clinical presentations. These diseases are slow progressing with late visible phenotypic characteristics and are often untreatable [ 1 ]. Most of our current knowledge on the etiology of neurodegenerative diseases comes from observational studies which suggest an underlying multifactorial etiology due to complex gene-environment interaction in patients suffering from non-monogenic disease subtypes [ 2 ].…”