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The document "Neurodegenerative Diseases: Molecular Mechanisms and Therapies 2nd Edition" published in the International Journal of Molecular Sciences discusses the prevalence, molecular pathogenesis, and therapeutic approaches for neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. It highlights recent advances in proteomics research, the use of 3D organoid models, machine learning in drug discovery, and emerging pharmacological treatments for these conditions. The text also explores the genetic factors, pathological mechanisms, and potential therapeutic targets associated with these diseases, emphasizing the need for innovative approaches to address the economic and societal burden they pose. [Extracted from the article]

A letter published in the journal "Obesity Facts: The European Journal of Obesity" discusses a study on the factors associated with constipation in people with obesity. The authors of the letter express interest in the study's findings but raise concerns about certain confounding variables that were not considered. They highlight the need for data on the use of laxatives and other medications, as well as the classification of hypertension used in the study. The authors suggest that a prospective longitudinal study with objective measurements would provide more conclusive evidence on the relationship between constipation, obesity, hypertension, and polypharmacy. [Extracted from the article]

Essential tremor (ET), one of the most common adult-onset movement disorders, has been associated with cerebellar Purkinje cell degeneration and formation of brainstem Lewy bodies. Recent findings suggest that genetic variants of the leucine-rich repeat and Ig domain containing 1 (LINGO-1) gene could be risk factors for ET. The LINGO-1 protein contains both leucine-rich repeat (LRR) and immunoglobulin (Ig)-like domains in its extracellular region, as well as a transmembrane domain and a short cytoplasmic tail. LINGO-1 can form a ternary complex with Nogo-66 receptor (NgR1) and p75. Binding of LINGO-1 with NgR1 can activate the NgR1 signaling pathway, leading to inhibition of oligodendrocyte differentiation and myelination in the central nervous system. LINGO-1 has also been found to bind with epidermal growth factor receptor (EGFR) and induce downregulation of the activity of EGFR–PI3K–Akt signaling, which might decrease Purkinje cell survival. Therefore, it is possible that genetic variants of LINGO-1, either alone or in combination with other genetic or environmental factors, act to increase LINGO-1 expression levels in Purkinje cells and confer a risk to Purkinje cell survival in the cerebellum. Here, we provide a concise summary of the link between LINGO-1 and neurodegeneration and discuss various hypotheses as to how this could be potentially relevant to ET pathogenesis.

Caffeine is one of the most consumed psychoactive substances globally. Caffeine-gene interactions in Parkinson's disease (PD) has not been systematically examined. To conduct a systematic review on the interaction between caffeine consumption and genetic susceptibility to PD. We conducted PubMed and Embase search using terms "Genetic association studies", "Caffeine", "polymorphism" and "Parkinson's disease", from inception till 2023. Of the initial 2391 studies, 21 case-control studies were included. The demographic, genetic and clinical data were extracted and analyzed. We identified 21 studies which involved a total of 607,074 study subjects and 17 gene loci (SNCA, MAPT, HLA-DRA, NOS1, NOS3, GBA, ApoE, BST1, ESR2, NAT2, SLC2A13, LRRK2, NOS2A, GRIN2A, CYP1A2, ESR1, ADORA2A) have been investigated for the effect of gene-caffeine interaction and PD risk. The genes were identified through PD GWAS or involved in caffeine or related metabolism pathways. Based on the genetic association and interaction studies, only MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2 , and ADORA2A have been shown by at least one study to have a positive caffeine-gene interaction influencing the risk of PD. Studies have shown an interaction between caffeine with genetic variants of MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2 , and ADORA2A in modulating the risk of PD. Due to the potential limitations of these discovery/pilot studies, further independent replication studies are needed. Better designed genetic association studies in multi-ancestry and admixed cohorts to identify potential shared or unique multivariate gene-environmental interactions, as well as functional studies of gene-caffeine interactions will be useful. [Display omitted] • Caffeine is one of the most consumed psychoactive substances globally. • Caffeine is an antagonist of adenosine A2A receptor and caffeine consumption can be protective against PD. • Results from 21 studies involving 607,074 human subjects and 17 gene loci are investigated to understand the interplay of caffeine and genetic factors in PD risk. • Eight genes, including MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2 , and ADORA2A , are identified to have a positive caffeine-gene interaction to influence PD risk. [ABSTRACT FROM AUTHOR]