Recent Advances in Alzheimer Research

Volume: 2

Amyloidogenic Peptide Structure, Aggregation, And Membrane Interaction

Author(s): Manoel Arcisio-Miranda and Laíz da Costa Silva-Gonçalves

Pp: 104-139 (36)

DOI: 10.2174/9781681087153118020007

* (Excluding Mailing and Handling)

Abstract

It is estimated that 44 millions of people have Alzheimer’s disease (AD) or related dementia around the world. The AD is an irreversible progressive brain disorder that destroys the memory and thinking and causes the loss of cognitive functions. The development of AD is strongly correlated with the development of plaques and tangles in the brain. Beta-amyloid (Aβ) peptides are the main compound in the brain plaques however, their neurotoxic effects remain unclear. These peptides are generated from Amyloid Precursor Protein (APP) and the APP processing may be modulated by many factors, such as lipid rafts. Aβ coexists in different forms in the brain and the exact neurotoxic effect of each one is not understood. The majority of the studies about Aβ neurotoxicity suggests that the fibrillar form is the most neurotoxic and for this reason, much effort has been employed to understand mechanisms that modulate or inhibit the fibrillation process. Other studies suggest that the main neurotoxic form is the oligomer, which forms channels in the lipid membrane and induces cell death. In this chapter, we explore the mechanism of Aβ’s production and fibrillation, and the factors that can modulate it.


Keywords: Aggregation, Amyloidogenesis, Amyloid Fibrils, Amyloid Inhibitors, APP, β-Amyloid Peptides, Membrane.

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      • 14. app/Models/Subject.php:238
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      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1465
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
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      300μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
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      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ChapterController.php:1478
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
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      630μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59694094 and j.to_ip >=59694094 )) and ((j.from_date <= 1739847145 and j.to_date >= 1739847145 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12529) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59694094 and j.to_ip >=59694094 )) and ((j.from_date <= 1739847145 and j.to_date >= 1739847145 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12529) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59694094 and j.to_ip >=59694094 )) and ((j.from_date <= 1739847145 and j.to_date >= 1739847145 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 12529)
      580μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1959 and `b`.`banner_from_date` <= 1739847145 and `b`.`banner_to_date` >= 1739847145 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.09msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1959
      • 3: 1739847145
      • 4: 1739847145
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='f59d6152ef70ff77b14a6b07aae56efa'
      240μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    7Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        hUo1W5iZRIxffxm0OvxBDUqWhntFUAKDWFIIiFgZ
        uc_cart_id
        f59d6152ef70ff77b14a6b07aae56efa
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12529" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/12529
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InhNMmJPbFhSSG9OYUcyVXRqa283NVE9PSIsInZhbHVlIjoiQjFCcVdVTHN5Y0dSYnEzWlZVY1Q4RFc1NTVZTFoxbzlsWllpVlVTUDNiTT0iLCJtYWMiOiJlNWEwZDUzYTQ5YmI3NWY5NDc4NjUxMTUxOTE3MzRkNWUxNzVkM2M0ZWRhNzc3NTU0NzEzMGIzNDVjYTllMzJjIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InhNMmJPbFhSSG9OYUcyVXRqa283NVE9PSIsInZhbHVlIjoiQjFCcVdVTHN5Y0dSYnEzWlZVY1Q4RFc1NTVZTFoxbzlsWllpVlVTUDNiTT0iLCJtYWMiOiJlNWEwZDUzYTQ5YmI3" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 18 Feb 2025 02:52:25 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IndTVTh3M1lxak1VRzFOcFp6YnVETnc9PSIsInZhbHVlIjoieDhkZEhmekloNEphNEhGbjZRckhIZEErZHRhS29ldy9ia2EyNUNpTXgvQ3dSWHdhV3J6dEU3d1ZocGRtazl1cTBuZm5EQVozNnpNYlRKa05hbDFVdmEvN3F2QWxuRUcvVlljaHVwWE9BZkRCUHB3UkF1eDZVNjdYVFg4MWphQUkiLCJtYWMiOiJjZGI5NTFlODg0NTQ4NjBlODAxMzU0OWQ4NDE1MWI1ZmE4YWQ5NjJiMDE2ZTI5M2M2ZDRmZjhlNDIwZmVkNGMzIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 14:52:25 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IndTVTh3M1lxak1VRzFOcFp6YnVETnc9PSIsInZhbHVlIjoieDhkZEhmekloNEphNEhGbjZRckhIZEErZHRhS29ldy9ia2EyNUNpTXgvQ3dSWHdhV3J6dEU3d1ZocGRtazl1cTBuZm5EQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlNlQk9SUXh6ZEVYZ1l6a0x2aGR4V2c9PSIsInZhbHVlIjoiM0hDUzNxMWk4Kzk3ZkVxWjhvdExjZFRzUGp4MHBjRml1Y2UyWllvaXF6ODhMTjNaakRMMDJ2OEtLT3UraVlkZU0xL3lBWkViL1F4d25WMWhpelVkZnpYYnd3eFlmZWhjcDRTazEyMnYvdE8xUmlJU285ZGZxL3U1cFQ2WFl4R2EiLCJtYWMiOiIxYTU5Y2E3OTJkYTRkN2FmNmE1OGEwZWI3MjZjODg2NDE3ZDQwNzhjZjFkNzEwNzg0MWFmMjVhYTkwNTI5ZTc4IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IlNlQk9SUXh6ZEVYZ1l6a0x2aGR4V2c9PSIsInZhbHVlIjoiM0hDUzNxMWk4Kzk3ZkVxWjhvdExjZFRzUGp4MHBjRml1Y2UyWllvaXF6ODhMTjNaakRMMDJ2OEt" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IndTVTh3M1lxak1VRzFOcFp6YnVETnc9PSIsInZhbHVlIjoieDhkZEhmekloNEphNEhGbjZRckhIZEErZHRhS29ldy9ia2EyNUNpTXgvQ3dSWHdhV3J6dEU3d1ZocGRtazl1cTBuZm5EQVozNnpNYlRKa05hbDFVdmEvN3F2QWxuRUcvVlljaHVwWE9BZkRCUHB3UkF1eDZVNjdYVFg4MWphQUkiLCJtYWMiOiJjZGI5NTFlODg0NTQ4NjBlODAxMzU0OWQ4NDE1MWI1ZmE4YWQ5NjJiMDE2ZTI5M2M2ZDRmZjhlNDIwZmVkNGMzIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 14:52:25 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IndTVTh3M1lxak1VRzFOcFp6YnVETnc9PSIsInZhbHVlIjoieDhkZEhmekloNEphNEhGbjZRckhIZEErZHRhS29ldy9ia2EyNUNpTXgvQ3dSWHdhV3J6dEU3d1ZocGRtazl1cTBuZm5EQ" 1 => "alphaeurekaselectnet_session=eyJpdiI6IlNlQk9SUXh6ZEVYZ1l6a0x2aGR4V2c9PSIsInZhbHVlIjoiM0hDUzNxMWk4Kzk3ZkVxWjhvdExjZFRzUGp4MHBjRml1Y2UyWllvaXF6ODhMTjNaakRMMDJ2OEtLT3UraVlkZU0xL3lBWkViL1F4d25WMWhpelVkZnpYYnd3eFlmZWhjcDRTazEyMnYvdE8xUmlJU285ZGZxL3U1cFQ2WFl4R2EiLCJtYWMiOiIxYTU5Y2E3OTJkYTRkN2FmNmE1OGEwZWI3MjZjODg2NDE3ZDQwNzhjZjFkNzEwNzg0MWFmMjVhYTkwNTI5ZTc4IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IlNlQk9SUXh6ZEVYZ1l6a0x2aGR4V2c9PSIsInZhbHVlIjoiM0hDUzNxMWk4Kzk3ZkVxWjhvdExjZFRzUGp4MHBjRml1Y2UyWllvaXF6ODhMTjNaakRMMDJ2OEt" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "hUo1W5iZRIxffxm0OvxBDUqWhntFUAKDWFIIiFgZ" "uc_cart_id" => "f59d6152ef70ff77b14a6b07aae56efa" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/12529" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 02:52:25GET/chapter/12529112199